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Doghish AS, Zaki MB, Hatawsh A, Elfar N, Alhamshry NAA, Abd-Elmawla MA, Aborehab NM, Radwan AF, Moussa R, Mageed SSA, Abdel-Reheim MA, Mohammed OA, Elimam H. Alternative medicines in oncology: a focus on natural products against gastric cancer. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04058-2. [PMID: 40261350 DOI: 10.1007/s00210-025-04058-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Accepted: 03/13/2025] [Indexed: 04/24/2025]
Abstract
There is justification for optimism about the potential contribution of alternative medicines to cancer management, which now ranks as the second leading cause of death globally. Primary carcinogens arise from several sources, including agriculture, industry, and dietary intake. Gastric cancer (GC) significantly affects an individual's health due to its classification as a malignant tumor associated with elevated mortality and morbidity rates. Chemotherapy is now widely regarded as the gold standard for treating GC. Chemotherapy, however, exerts significant detrimental effects on human health, including irreversible damage to multiple organs. Consequently, it is essential to employ innovative strategies for cancer prevention. Natural products are now the focus of intensive study due to their efficacy against cancer and low toxicity levels. Natural compounds have shown a diverse range of anti-cancer properties. This review aims to emphasize studies on natural compounds that inhibit metastasis, induce apoptosis in GC, and decrease cellular proliferation. All the natural compounds from different sources were incorporated in this review not only medicinal plants derived compounds. This review aims to examine a comprehensive array of natural therapies that may enhance human health and facilitate GC prevention without inducing discernible negative effects. Moreover, this review aims to discuss the toxic side effects of phytochemicals and shed light on mechanisms underlying the action of potential natural products against GC. This review offers a novel perspective by integrating a broad spectrum of natural compounds from diverse sources, not limited to medicinal plants, to explore their anti-cancer properties against gastric cancer.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt
- Department of Biochemistry, Faculty of Pharmacy, Menoufia National University, km Cairo-Alexandria Agricultural Road, Menofia, Egypt
| | - Abdulrahman Hatawsh
- Biotechnology School, Nile University, 26th of July Corridor, Sheikh Zayed City, Giza, 12588, Egypt
| | - Nourhan Elfar
- School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo, 11578, Egypt
- Egyptian Drug Authority (EDA), Ministry of Health and Population, Cairo, 11567, Egypt
| | - Nora A A Alhamshry
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt
| | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Nora M Aborehab
- Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt
| | - Abdullah F Radwan
- Department of Pharmacy, Kut University College, Al Kut, Wasit, 52001, Iraq
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, 11829, Egypt
| | - Rewan Moussa
- Faculty of Medicine, Helwan University, Cairo, 11795, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Mustafa Ahmed Abdel-Reheim
- Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, 11961, Saudi Arabia.
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia
| | - Hanan Elimam
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt.
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Avula SK, Ullah S, Ebrahimi A, Rostami A, Halim SA, Khan A, Anwar MU, Gibbons S, Csuk R, Al-Harrasi A. Dihydrofolate reductase inhibitory potential of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as new anticancer derivatives: In-vitro and in-silico studies. Eur J Med Chem 2025; 283:117174. [PMID: 39708770 DOI: 10.1016/j.ejmech.2024.117174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 11/24/2024] [Accepted: 12/03/2024] [Indexed: 12/23/2024]
Abstract
In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety. The resulting compounds have been screened for their dihydrofolate reductase (DHFR) inhibition activity. All the newly synthesized compounds were characterized by 1H NMR, 13C NMR, 19F NMR (spectroscopy when applicable), and HR-ESI-MS spectroscopy techniques. The X-ray crystallography studies have unambiguously confirmed the structure of compounds 6, 11 and 13. Furthermore, their DHFR-inhibitory activity was evaluated in-vitro. The results obtained from the DHFR-inhibitory assay revealed that all the synthesized 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives were highly potent inhibitors, with IC50 values in the range 3.48 ± 0.16-30.37 ± 1.20 μM. Ten compounds (15c-15f, 16c-16f, 17e and 17f) among the 32 synthesized 1H-indole-based-meldrum linked 1H-1,2,3-triazole compounds were found to exhibit exceptional inhibitory while the rest of the derivatives showed moderate activities. Additionally, molecular docking analysis of the most active (16f), moderate (15c) and least active (16a) inhibitors reflect excellent binding of 16f with the binding residues of DHFR with higher docking score (-9.13 kcal/mol) than that of 15c and 16a. The docking analysis correlates well with the inhibitory potential of these synthesized molecules. Overall, this study may pave the way to medicinal analogues of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as potent DHFR inhibition activity.
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Affiliation(s)
- Satya Kumar Avula
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman.
| | - Saeed Ullah
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman
| | - Amirhossein Ebrahimi
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman
| | - Ali Rostami
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman
| | - Sobia Ahsan Halim
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman
| | - Ajmal Khan
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman
| | - Muhammad U Anwar
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman
| | - Simon Gibbons
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman
| | - René Csuk
- Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120, Halle, Saale, Germany
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman.
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El-Tanbouly R, Hassan H, Awd LM, Makhlouf AA, Shalabi HG, El-Messeiry S. Molecular validation of genetically transformed Catharanthus roseus plants via different strains of Agrobacterium tumefaciens. Heliyon 2024; 10:e40589. [PMID: 39654749 PMCID: PMC11626052 DOI: 10.1016/j.heliyon.2024.e40589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 09/29/2024] [Accepted: 11/19/2024] [Indexed: 12/12/2024] Open
Abstract
Medical plants play a crucial role in the pharmaceutical industry due to their natural synthesis of active compounds. Synthetic methods exist, which provide fewer effective molecules compared to those naturally occurring. Catharanthus roseus, a significant medicinal plant, synthesizes vital vinca alkaloids and various secondary metabolites widely used in cancer and hypertension treatment. However, genetic modification using Agrobacterium tumefaciens-mediated transformation, a common method for altering periwinkle plants, suffers from low efficiency and reproducibility. Factors like the Agrobacterium strain can influence transformation efficiency and post-transformation regeneration. This study compares the transformation and regeneration efficiency of three A. tumefaciens strains (LBA4404, EHA105, and GV3101) carrying the GUS gene and kanamycin selection via syringe infiltration in Catharanthus roseus. Molecular variations between mutants were examined using Inter-Simple Sequence Repeat (ISSR) and GUS expression via quantitative Real-Time PCR (qRT-PCR). Results revealed that GV3101 had the highest transformation efficiency (61.1 %) and LBA4404 the lowest (38 %). However, GV3101-infected explants had the lowest regeneration rate (10 %), the obtained mutants from it exhibited the highest GUS expression. ISSR analysis indicated 37 % polymorphism among mutants, highlighting the impact of Agrobacterium strains on plant genetics and potentially on phytochemical compositions. Overall, this study recommends using GV3101 for high transformation efficiency and LBA4404 for superior in vitro regeneration in Catharanthus roseus, suggesting a promising method for efficient gene transformation in this plant species.
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Affiliation(s)
- Rania El-Tanbouly
- Department of Floriculture, Ornamental Horticulture and Landscape Design, Faculty of Agriculture, Alexandria University, 163 Aflaton Street, El Shatby, Alexandria, 21545, Egypt
| | - Hend Hassan
- Department of Floriculture, Ornamental Horticulture and Landscape Design, Faculty of Agriculture, Alexandria University, 163 Aflaton Street, El Shatby, Alexandria, 21545, Egypt
| | - Lojina M. Awd
- Department of Genetics, Faculty of Agriculture, Alexandria University, 163 Aflaton Street, El Shatby, Alexandria, 21545, Egypt
| | - Azza Ali Makhlouf
- Department of Genetics, Faculty of Agriculture, Alexandria University, 163 Aflaton Street, El Shatby, Alexandria, 21545, Egypt
| | - Hani G. Shalabi
- Department of Genetics, Faculty of Agriculture, Alexandria University, 163 Aflaton Street, El Shatby, Alexandria, 21545, Egypt
| | - Sarah El-Messeiry
- Department of Genetics, Faculty of Agriculture, Alexandria University, 163 Aflaton Street, El Shatby, Alexandria, 21545, Egypt
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Hemanth C, Vimal S. Assessment of Anti-oxidative, Anti-inflammatory, and Anti-cancer Activity of Magnesium Oxide Doped Chitosan/Polyvinyl Alcohol With Catharanthus roseus: An In Vitro Study. Cureus 2024; 16:e70103. [PMID: 39449928 PMCID: PMC11500816 DOI: 10.7759/cureus.70103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 07/29/2024] [Indexed: 10/26/2024] Open
Abstract
Background Recent biomedical research has emphasized the potential of biocomposite materials for medicinal purposes. This work investigates the combination of magnesium oxide (MgO)-doped chitosan and polyvinyl alcohol (PVA) with extracts from Catharanthus roseus, a medicinal plant renowned for its abundant alkaloid content and therapeutic advantages. The antioxidant, anti-inflammatory, and anti-cancer characteristics of this unique biocomposite material are being studied better to understand its prospective uses in biomedicine. Aim The goal of this study is to investigate the in vitro oxidative, anti-inflammatory, and anti-cancer properties of a biocomposite made of MgO-doped chitosan and PVA, combined with an extract from C. roseus. Materials and methods The biocomposite was made by blending chitosan and PVA in equal proportions and adding MgO nanoparticles to C. roseus extract. The surface morphology was analysed using scanning electron microscopy (SEM). The antioxidant activity was measured using the H2O2 test, the anti-inflammatory activity was identified using the egg albumin assay, and the anti-cancer activity was analyzed using the MTT assay on MCF-7 breast cancer cell lines. In addition, cell morphology investigations were performed to evaluate any alterations after treatment. Results The SEM investigation showed clearly defined and sleek nanoparticles. The biocomposite demonstrated notable antioxidant activity, with inhibition percentages escalating in proportion to the concentration. The anti-inflammatory assays demonstrated inhibition percentages comparable to diclofenac, reaching approximately 90% at the maximum concentration. The MTT experiment revealed that the viability of MCF-7 cells decreased in a manner that was dependent on the dose administered. The IC-50 value, which represents the concentration required to inhibit 50% of cell viability, was determined to be 60 µg/mL. The morphological examinations demonstrated cytotoxic effects, such as cell shrinkage and membrane blebbing, which indicate the successful initiation of apoptosis. Conclusion The biocomposite of chitosan/PVA doped with MgO, combined with C. roseus extract, has shown significant antioxidant, anti-inflammatory, and anti-cancer characteristics. These findings indicate that it has the potential to be used in therapy, particularly for treating illnesses related to oxidative stress, inflammatory disorders, and cancer. Future research should focus on improving formulation and delivery systems for therapeutic applications, with the support of in vivostudies and clinical trials.
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Affiliation(s)
- Challa Hemanth
- Biochemistry, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
| | - Sugumar Vimal
- Biochemistry, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
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Srivastava G, Mittal R, Srivastava N, Ganjewala D. Exploring the potential of two Pseudomonas species to produce vincristine from vinblastine via biotransformation. Sci Rep 2024; 14:19652. [PMID: 39179785 PMCID: PMC11344160 DOI: 10.1038/s41598-024-70571-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 08/19/2024] [Indexed: 08/26/2024] Open
Abstract
A biotransformation pair consisting of vinblastine: vincristine present in the Catharanthus roseus plant is of immense pharmacological significance. In this study, we successfully transformed vinblastine into vincristine outside the plant using Pseudomonas aeruginosa 8485 and Pseudomonas fluorescens 2421 and evaluated the antiangiogenic potential of thus produced vincristine through the CAM assay. The toxicity assay showed that both Pseudomonas spp. can tolerate varying concentrations (25-100 µl of 1 mg/ml) of vinblastine. The biotransformation was performed in a liquid nutrient broth medium containing vinblastine (25-100 µl), and Pseudomonas spp. inoculums (50-150 µl) by incubating at 30 °C and 37 °C, respectively for 8 days. The process was optimized for substrate and culture concentrations, pH, temperature, and rotation speed (rpm) for the highest conversion. Analysis using LC-MS/MS confirmed the presence of vincristine as a product of the vinblastine biotransformation by two Pseudomonas spp. P. fluorescens 2421 showed a faster conversion rate with 95% of vinblastine transformed within 24 h than P. aeruginosa 8485, which demonstrated a conversion rate of 92% on the 8th day. From LC-MS/MS analysis, the optimal conditions for the reaction were determined as vinblastine (25 µl), microbial inoculums (150 µl or 200 × 106 and 210 × 106 CFU/ml), pH 7.4, rotation speed of 180 rpm, and temperatures of 30 °C and 37 °C with incubation time of 8 days. The vincristine produced exhibited potent antiangiogenic activity in the CAM assay reducing the thickness and branching of blood vessels in a dose-dependent manner. The study concludes that both Pseudomonas spp. showed promise for vincristine production from vinblastine, without compromising its antiangiogenic properties.
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Affiliation(s)
- Gauri Srivastava
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector-125, Noida, UP, 201303, India
| | - Ruchika Mittal
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector-125, Noida, UP, 201303, India
| | - Nidhi Srivastava
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector-125, Noida, UP, 201303, India
| | - Deepak Ganjewala
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector-125, Noida, UP, 201303, India.
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Zhang QQ, Jin F, Yu JH, Zhang C, Zhang M, Deng MZ, Lin SX, Chen L, Zhao YL, He B, Li Y. Preparation of Indolin-3-one-Containing 1,4-Naphthoquinone Derivatives via Organocatalytic Asymmetric Michael Addition Reaction. J Org Chem 2024; 89:10099-10111. [PMID: 38943598 DOI: 10.1021/acs.joc.4c00956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.
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Affiliation(s)
- Qing-Qing Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Fei Jin
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Jun-Hui Yu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Chuang Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Mao Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Ming-Zhenlong Deng
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Shu-Xian Lin
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Lei Chen
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Yong-Long Zhao
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Bin He
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
| | - Yan Li
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China
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Chen H, Sahu SK, Wang S, Liu J, Yang J, Cheng L, Chiu TY, Liu H. Chromosome-level Alstonia scholaris genome unveils evolutionary insights into biosynthesis of monoterpenoid indole alkaloids. iScience 2024; 27:109599. [PMID: 38646178 PMCID: PMC11033161 DOI: 10.1016/j.isci.2024.109599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 01/25/2024] [Accepted: 03/25/2024] [Indexed: 04/23/2024] Open
Abstract
Alstonia scholaris of the Apocynaceae family is a medicinal plant with a rich source of bioactive monoterpenoid indole alkaloids (MIAs), which possess anti-cancer activity like vinca alkaloids. To gain genomic insights into MIA biosynthesis, we assembled a high-quality chromosome-level genome for A. scholaris using nanopore and Hi-C data. The 444.95 Mb genome contained 35,488 protein-coding genes. A total of 20 chromosomes were assembled with a scaffold N50 of 21.75 Mb. The genome contained a cluster of strictosidine synthases and tryptophan decarboxylases with synteny to other species and a saccharide-terpene cluster involved in the monoterpenoid biosynthesis pathway of the MIA upstream pathway. The multi-omics data of A. scholaris provide a valuable resource for understanding the evolutionary origins of MIAs and for discovering biosynthetic pathways and synthetic biology efforts for producing pharmaceutically useful alkaloids.
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Affiliation(s)
- Haixia Chen
- State Key Laboratory of Agricultural Genomics, Key Laboratory of Genomics, Ministry of Agriculture, BGI Research, Shenzhen 518083, China
- BGI Research, Wuhan 430074, China
| | - Sunil Kumar Sahu
- State Key Laboratory of Agricultural Genomics, Key Laboratory of Genomics, Ministry of Agriculture, BGI Research, Shenzhen 518083, China
- BGI Research, Wuhan 430074, China
| | - Shujie Wang
- State Key Laboratory of Agricultural Genomics, Key Laboratory of Genomics, Ministry of Agriculture, BGI Research, Shenzhen 518083, China
| | - Jia Liu
- Key Laboratory of Soybean Molecular Design Breeding, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Harbin 150081, China
| | - Jinlong Yang
- State Key Laboratory of Agricultural Genomics, Key Laboratory of Genomics, Ministry of Agriculture, BGI Research, Shenzhen 518083, China
| | - Le Cheng
- State Key Laboratory of Agricultural Genomics, Key Laboratory of Genomics, Ministry of Agriculture, BGI Research, Shenzhen 518083, China
| | - Tsan-Yu Chiu
- State Key Laboratory of Agricultural Genomics, Key Laboratory of Genomics, Ministry of Agriculture, BGI Research, Shenzhen 518083, China
| | - Huan Liu
- State Key Laboratory of Agricultural Genomics, Key Laboratory of Genomics, Ministry of Agriculture, BGI Research, Shenzhen 518083, China
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Nabaei M, Amooaghaie R, Ghorbanpour M, Ahadi A. Crosstalk between melatonin and nitric oxide restrains Cadmium-induced oxidative stress and enhances vinblastine biosynthesis in Catharanthus roseus (L) G Don. PLANT CELL REPORTS 2024; 43:139. [PMID: 38735908 DOI: 10.1007/s00299-024-03229-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 05/02/2024] [Indexed: 05/14/2024]
Abstract
KEY MESSAGE Nitric oxide functions downstream of the melatonin in adjusting Cd-induced osmotic and oxidative stresses, upregulating the transcription of D4H and DAT genes, and increasing total alkaloid and vincristine contents. A few studies have investigated the relationship between melatonin (MT) and nitric oxide (NO) in regulating defensive responses. However, it is still unclear how MT and NO interact to regulate the biosynthesis of alkaloids and vincristine in leaves of Catharanthus roseus (L.) G. Don under Cd stress. Therefore, this context was explored in the present study. Results showed that Cd toxicity (200 µM) induced oxidative stress, decreased biomass, Chl a, and Chl b content, and increased the content of total alkaloid and vinblastine in the leaves. Application of both MT (100 µM) and sodium nitroprusside (200 µM SNP, as NO donor) enhanced endogenous NO content and accordingly increased metal tolerance index, the content of total alkaloid and vinblastine. It also upregulated the transcription of two respective genes (D4H and DAT) under non-stress and Cd stress conditions. Moreover, the MT and SNP treatments reduced the content of H2O2 and malondialdehyde, increased the activities of superoxide dismutase and ascorbate peroxidase, enhanced proline accumulation, and improved relative water content in leaves of Cd-exposed plants. The scavenging NO by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy l-3-oxide (cPTIO) averted the effects of MT on the content of total alkaloid and vinblastine and antioxidative responses. Still, the effects conferred by NO on attributes mentioned above were not significantly impaired by p-chlorophenylalanine (p-CPA as an inhibitor of MT biosynthesis). These findings and multivariate analyses indicate that MT motivated terpenoid indole alkaloid biosynthesis and mitigated Cd-induced oxidative stress in the leaves of periwinkle in a NO-dependent manner.
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Affiliation(s)
- Masoomeh Nabaei
- Plant Science Department, Faculty of Science, Shahrekord University, Shahrekord, Iran
| | - Rayhaneh Amooaghaie
- Plant Science Department, Faculty of Science, Shahrekord University, Shahrekord, Iran.
- Biotechnology Research Institute, Shahrekord University, Shahrekord, Iran.
| | - Mansour Ghorbanpour
- Department of Medicinal Plants, Faculty of Agriculture and Natural Resources, Arak University, Arak, 38156-8-8349, Iran
| | - Alimohammad Ahadi
- Genetic Department, Science Faculty, Shahrekord University, Shahrekord, Iran
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Silva VBD, Almeida-Bezerra JW, Novais MHG, Farias NS, Coelho JJ, Ribeiro PRV, Canuto KM, Coutinho HDM, Morais-Braga MFB, Oliveira AFMD. Chemical composition, antifungal, and anti-virulence action of the stem bark of Hancornia speciosa Gomes (Apocynaceae) against Candida spp. JOURNAL OF ETHNOPHARMACOLOGY 2024; 321:117506. [PMID: 38012976 DOI: 10.1016/j.jep.2023.117506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/17/2023] [Accepted: 11/22/2023] [Indexed: 11/29/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hancornia speciosa Gomes is a fruit and medicinal species used for treating infectious diseases of the genitourinary system. However, its mechanism of action against microbes is still not fully understood. Infections in the genitourinary system caused by Candida spp. are associated with its fungal resistance and pathogenicity. New plant-derived compounds are an alternative to fight these Candida infections. AIM OF THE STUDY The objective of this study was to evaluate the anti-Candida effects of extracts of the stem bark of H. speciosa. This research investigated the chemical composition of sulfuric ether (EEHS) and methanolic (MEHS) extracts, their drug-modifying action on fluconazole, and their anti-virulence action on the morphological transition of Candida species. MATERIALS AND METHODS The extracts (EEHS and MEHS) of the stem bark of H. speciosa were chemically characterized via qualitative phytochemical screening and by liquid chromatography coupled with mass spectrometry (UPLC-MS-ESI-QTOF). The extracts were evaluated regarding their antifungal effects and fluconazole-modifying activity against Candida albicans, Candida krusei, and Candida tropicalis using the broth microdilution method. Additionally, the study evaluated the inhibition of fungal virulence in Candida species through morphological transition assays. RESULTS The phytochemical screening revealed the presence of anthocyanidins, anthocyanins, aurones, catechins, chalcones, flavones, flavonols, flavanones, leucoanthocyanidins, tannins (condensed and pyrogallic), and xanthones in both extracts of the stem bark of H. speciosa. The UPLC-MS-ESI-QTOF analysis identified the same compounds in both extracts, predominating phenolic compounds. Some compounds were first time recorded in this species: gluconic acid, cinchonain IIb, cinchonain Ib isomer, and lariciresinol hexoside isomers. Most of the intrinsic antifungal activity was observed for the MEHS against C. krusei (IC50: 58.41 μg/mL). At subinhibitory concentrations (MC/8), the EEHS enhanced the action of fluconazole against all Candida strains. The MEHS exhibited greater efficacy than fluconazole inhibiting C. krusei growth. The EEHS completely inhibited hyphae appearance and reduced pseudohyphae formation in C. albicans. CONCLUSION The stem bark of H. speciosa is a rich source of bioactive compounds, especially phenolic. Phenolic compounds can have important roles in fighting infectious diseases of the genitourinary system, such as candidiasis. The extracts of H. speciosa improved the action of the drug fluconazole against Candida species, inhibited hyphae appearance, and reduced pseudohyphae formation. The results of this study can support the development of new therapeutics against resistant strains of Candida.
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Affiliation(s)
- Viviane Bezerra da Silva
- Department of Botany, Universidade Federal de Pernambuco - UFPE, Rua Professor Moraes Rego, s/n, Recife, Pernambuco, 50.670-901, Brazil.
| | - José Weverton Almeida-Bezerra
- Department of Botany, Universidade Federal de Pernambuco - UFPE, Rua Professor Moraes Rego, s/n, Recife, Pernambuco, 50.670-901, Brazil
| | - Maria Hellena Garcia Novais
- Department of Biological Sciences, Universidade Regional do Cariri - URCA, Rua Cel. Antônio Luiz, 1161, Crato, Ceará, 63.105-000, Brazil
| | - Naiza Saraiva Farias
- Department of Biological Sciences, Universidade Regional do Cariri - URCA, Rua Cel. Antônio Luiz, 1161, Crato, Ceará, 63.105-000, Brazil
| | - Janerson José Coelho
- Animal Science Department, Universidade Estadual do Maranhão - UEMA, São Luís, Maranhão, Brazil
| | - Paulo Riceli Vasconcelos Ribeiro
- Multi-User Natural Products Chemistry Laboratory - LMQPN, Embrapa Agroindustria Tropical, Rua Dra. Sara Mesquita, 2270, Fortaleza, Ceará, 60511-110, Brazil
| | - Kirley Marques Canuto
- Multi-User Natural Products Chemistry Laboratory - LMQPN, Embrapa Agroindustria Tropical, Rua Dra. Sara Mesquita, 2270, Fortaleza, Ceará, 60511-110, Brazil
| | - Henrique Douglas Melo Coutinho
- Department of Biological Chemistry, Universidade Regional do Cariri - URCA, Rua Cel. Antônio Luiz, 1161, Crato, Ceará, 63.105-000, Brazil
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10
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Shukla R, Singh A, Singh KK. Vincristine-based nanoformulations: a preclinical and clinical studies overview. Drug Deliv Transl Res 2024; 14:1-16. [PMID: 37552393 PMCID: PMC10746576 DOI: 10.1007/s13346-023-01389-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2023] [Indexed: 08/09/2023]
Abstract
Vincristine (VCR) is a chemotherapeutic agent obtained from natural alkaloid plant source Catharanthus roseus. VCR has been significantly useful in treatments of lung cancer, lymphocyte-based leukaemia, glioblastomas and acute myeloid leukaemia. VCR attaches to tubulin fibrils and prevents filament polymerization that permanently led to mitosis inhibition in cancer cells. Clinically, VCR is administered to patients in multidrug combination to reduce adverse drug effects and potential blockage of bone marrow inhibition due to prescribed monotherapy. However, VCR possesses low cancer tissue affinity and at higher dose often led to irreversible neurotoxicity. Conventional VCR injectables are successfully used in clinics, but lack of controlled release, non-specific biodistribution and consequent off-target side effects are still major challenges. Currently, nanotechnological drug delivery systems are being explored for improvement of VCR pharmacokinetic profile and tumour-specific targeting. Various nanomedicine formulations such as liposomes, lipid nanoparticles, and polymeric nanocarriers of VCR have been studied under various in vitro and in vivo models. In this review, we have summarised the chemotherapeutic role of VCR, evaluated the mechanism of action, pharmacokinetics and challenges associated with VCR delivery. Moreover, application of VCR in nanomedicine and effect on anticancer efficacy in preclinical and clinical setting are also being discussed.
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Affiliation(s)
- Rahul Shukla
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Raebareli, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, U.P, 226002, Lucknow, India.
| | - Ajit Singh
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Raebareli, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, U.P, 226002, Lucknow, India
| | - Kamalinder K Singh
- School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.
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11
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Rohilla S, Goyal G, Berwal P, Mathur N. A Review on Indole-triazole Molecular Hybrids as a Leading Edge in Drug Discovery: Current Landscape and Future Perspectives. Curr Top Med Chem 2024; 24:1557-1588. [PMID: 38766822 DOI: 10.2174/0115680266307132240509065351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 04/02/2024] [Accepted: 04/09/2024] [Indexed: 05/22/2024]
Abstract
Molecular hybridization is a rational design strategy used to create new ligands or prototypes by identifying and combining specific pharmacophoric subunits from the molecular structures of two or more known bioactive derivatives. Molecular hybridization is a valuable technique in drug discovery, enabling the modulation of unwanted side effects and the creation of potential dual-acting drugs that combine the effects of multiple therapeutic agents. Indole-triazole conjugates have emerged as promising candidates for new drug development. The indole and triazole moieties can be linked through various synthetic strategies, such as click chemistry or other coupling reactions, to generate a library of diverse compounds for biological screening. The achievable structural diversity with indole-triazole conjugates offers avenues to optimize their pharmacokinetic and pharmacodynamic attributes, amplifying their therapeutic efficacy. Researchers have extensively tailored both indole and triazole frameworks with diverse modifications to comprehend their impact on the drug's pharmacokinetic and pharmacodynamic characteristics. The current review article endeavours to explore and discuss various research strategies to design indoletriazole hybrids and elucidate their significance in a variety of pathological conditions. The insights provided herein are anticipated to be beneficial for the researchers and will likely encourage further exploration in this field.
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Affiliation(s)
- Suman Rohilla
- Department of Pharmaceutical Chemistry, SGT College of Pharmacy, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana, India
| | - Garima Goyal
- Department of Pharmaceutical Chemistry, SGT College of Pharmacy, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana, India
| | - Paras Berwal
- Department of Pharmaceutical Chemistry, SGT College of Pharmacy, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana, India
| | - Nancy Mathur
- Department of Pharmaceutical Chemistry, SGT College of Pharmacy, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana, India
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12
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Mishra S, Sahu A, Kaur A, Kaur M, Kumar J, Wal P. Recent Development in the Search for Epidermal Growth Factor Receptor (EGFR) Inhibitors based on the Indole Pharmacophore. Curr Top Med Chem 2024; 24:581-613. [PMID: 37909440 DOI: 10.2174/0115680266264206231020111820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 09/05/2023] [Accepted: 09/13/2023] [Indexed: 11/03/2023]
Abstract
The signal transduction and cell proliferation are regulated by the epidermal growth factor receptor. The proliferation of tumor cells, apoptosis, invasion, and angiogenesis is inhibited by the epidermal growth factor receptor. Thus, breast cancer, non-small cell lung cancer, cervical cancer, glioma, and bladder cancer can be treated by targeting the epidermal growth factor receptor. Although third-generation epidermal growth factor receptor inhibitors are potent drugs, patients exhibit drug resistance after treatment. Thus, the search for new drugs is being continued. Among the different potent epidermal growth factor receptor inhibitors, we have reviewed the indole-based inhibitors. We have discussed the structure-activity relationship of the compounds with the active sites of the epidermal growth factor receptor receptors, their synthesis, and molecular docking studies.
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Affiliation(s)
- Shweta Mishra
- SGT College of Pharmacy, SGT University, Gurugram, Haryana, 122505, India
| | - Adarsh Sahu
- Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya (A Central University), Sagar, 473003, Madhya Pradesh, India
- Amity Institute of Pharmacy, Amity University Rajasthan, NH11C Kant Kanwar Jaipur, 300202, India
| | - Avneet Kaur
- SGT College of Pharmacy, SGT University, Gurugram, Haryana, 122505, India
| | | | - Jayendra Kumar
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology, Delhi-NCR Campus, Ghaziabad, UP, 201204, India
| | - Pranay Wal
- Pranveer Singh Institute of Technology, Pharmacy, Kanpur, UP, India
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13
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Verdú-Navarro F, Moreno-Cid JA, Weiss J, Egea-Cortines M. The advent of plant cells in bioreactors. FRONTIERS IN PLANT SCIENCE 2023; 14:1310405. [PMID: 38148861 PMCID: PMC10749943 DOI: 10.3389/fpls.2023.1310405] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 12/01/2023] [Indexed: 12/28/2023]
Abstract
Ever since agriculture started, plants have been bred to obtain better yields, better fruits, or sustainable products under uncertain biotic and abiotic conditions. However, a new way to obtain products from plant cells emerged with the development of recombinant DNA technologies. This led to the possibility of producing exogenous molecules in plants. Furthermore, plant chemodiversity has been the main source of pharmacological molecules, opening a field of plant biotechnology directed to produce high quality plant metabolites. The need for different products by the pharma, cosmetics agriculture and food industry has pushed again to develop new procedures. These include cell production in bioreactors. While plant tissue and cell culture are an established technology, beginning over a hundred years ago, plant cell cultures have shown little impact in biotechnology projects, compared to bacterial, yeasts or animal cells. In this review we address the different types of bioreactors that are currently used for plant cell production and their usage for quality biomolecule production. We make an overview of Nicotiana tabacum, Nicotiana benthamiana, Oryza sativa, Daucus carota, Vitis vinifera and Physcomitrium patens as well-established models for plant cell culture, and some species used to obtain important metabolites, with an insight into the type of bioreactor and production protocols.
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Affiliation(s)
- Fuensanta Verdú-Navarro
- Bioprocessing R&D Department, Bionet, Parque Tecnológico Fuente Álamo, Fuente Álamo, Spain
- Genética Molecular, Instituto de Biotecnología Vegetal, Universidad Politécnica de Cartagena, Cartagena, Spain
| | - Juan A. Moreno-Cid
- Bioprocessing R&D Department, Bionet, Parque Tecnológico Fuente Álamo, Fuente Álamo, Spain
| | - Julia Weiss
- Genética Molecular, Instituto de Biotecnología Vegetal, Universidad Politécnica de Cartagena, Cartagena, Spain
| | - Marcos Egea-Cortines
- Genética Molecular, Instituto de Biotecnología Vegetal, Universidad Politécnica de Cartagena, Cartagena, Spain
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14
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Al Amin M, Emran TB, Khan J, Zehravi M, Sharma I, Patil A, Gupta JK, Jeslin D, Krishnan K, Das R, Nainu F, Ahmad I, Wilairatana P. Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment. Cancers (Basel) 2023; 15:5311. [PMID: 38001572 PMCID: PMC10670446 DOI: 10.3390/cancers15225311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 10/25/2023] [Accepted: 11/03/2023] [Indexed: 11/26/2023] Open
Abstract
Cancer is the leading cause of morbidity and mortality in people throughout the world. There are many signaling pathways associated with cancerous diseases, from which the Mitogen-activated protein kinase (MAPK) pathway performs a significant role in this regard. Apoptosis and proliferation are correlated with MAPK signaling pathways. Plenty of experimental investigations were carried out to assess the role of indole alkaloids in MAPK-mediated cancerous diseases. Previous reports established that indole alkaloids, such as vincristine and evodiamine are useful small molecules in cancer treatment via the MAPK signaling system. Indole alkaloids have the anticancer potential through different pathways. Vincristine and evodiamine are naturally occurring indole alkaloids that have strong anticancer properties. Additionally, much research is ongoing or completed with molecules belonging to this group. The current review aims to evaluate how indole alkaloids affect the MAPK signaling pathway in cancer treatment. Additionally, we focused on the advancement in the role of indole alkaloids, with the intention of modifying the MAPK signaling pathways to investigate potential new anticancer small molecules. Furthermore, clinical trials with indole alkaloids in cancer treatment are also highlighted.
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Affiliation(s)
- Md. Al Amin
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh;
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh;
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, USA
| | - Jishan Khan
- Department of Pharmacy, International Islamic University Chittagong, Kumira, Chittagong 4318, Bangladesh
| | - Mehrukh Zehravi
- Department of Clinical Pharmacy, College of Dentistry & Pharmacy, Buraydah Private Colleges, Buraydah 51418, Saudi Arabia;
| | - Indu Sharma
- Department of Physics, Career Point University, Hamirpur 176041, Himachal Pradesh, India
| | - Anasuya Patil
- Department of Pharmaceutics, KLE College of Pharmacy, Bengaluru 560010, Karnataka, India
| | - Jeetendra Kumar Gupta
- Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura 281406, Uttar Pradesh, India;
| | - D. Jeslin
- Department of Pharmaceutics, Sree Balaji Medical College and Hospital Campus, Bharath Institute of Higher Education and Research, Chromepet, Chennai 600044, Tamil Nadu, India
| | - Karthickeyan Krishnan
- Department of Pharmacy Practice, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai 600117, Tamil Nadu, India;
| | - Rajib Das
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia;
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61411, Saudi Arabia
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
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15
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Tonk D, Mujib A, Maqsood M, Khusrau M, Alsughayyir A, Dewir YH. Fungal Elicitation Enhances Vincristine and Vinblastine Yield in the Embryogenic Tissues of Catharanthus roseus. PLANTS (BASEL, SWITZERLAND) 2023; 12:3373. [PMID: 37836112 PMCID: PMC10574240 DOI: 10.3390/plants12193373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/17/2023] [Accepted: 09/20/2023] [Indexed: 10/15/2023]
Abstract
Fungal elicitation could improve the secondary metabolite contents of in vitro cultures. Herein, we report the effect of Fusarium oxysporum on vinblastine and vincristine alkaloid yields in Catharanthus roseus embryos. The study revealed increased yields of vinblastine and vincristine in Catharanthus tissues. Different concentrations, i.e., 0.05% (T1), 0.15% (T2), 0.25% (T3), and 0.35% (T4), of an F. oxysporum extract were applied to a solid MS medium in addition to a control (T0). Embryogenic calli were formed from the hypocotyl explants of germinating seedlings, and the tissues were exposed to Fusarium extract elicitation. The administration of the F. oxysporum extract improved the growth of the callus biomass, which later differentiated into embryos, and the maximum induction of somatic embryos was noted T2 concentration (102.69/callus mass). A biochemical analysis revealed extra accumulations of sugar, protein, and proline in the fungus-elicitated cultivating tissues. The somatic embryos germinated into plantlets on full-strength MS medium supplemented with 2.24 µM of BA. The germination rate of the embryos and the shoot and root lengths of the embryos were high at low doses of the Fusarium treatment. The yields of vinblastine and vincristine were measured in different treated tissues via high-pressure thin-layer chromatography (HPTLC). The yield of vinblastine was high in mature (45-day old) embryos (1.229 µg g-1 dry weight), which were further enriched (1.267 µg g-1 dry weight) via the F. oxysporum-elicitated treatment, especially at the T2 concentration. Compared to vinblastine, the vincristine content was low, with a maximum of 0.307 µg g-1 dry weight following the addition of the F. oxysporum treatment. The highest and increased yields of vinblastine and vincristine, 7.88 and 15.50%, were noted in F. oxysporum-amended tissues. The maturated and germinating somatic embryos had high levels of SOD activity, and upon the addition of the fungal extracts, the enzyme's activity was further elevated, indicating that the tissues experienced cellular stress which yielded increased levels of vinblastine and vincristine following the T2/T1 treatments. The improvement in the yields of these alkaloids could augment cancer healthcare treatments, making them easy, accessible, and inexpensive.
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Affiliation(s)
- Dipti Tonk
- Cellular Differentiation and Molecular Genetics Section, Department of Botany, Jamia Hamdard, New Delhi 110062, India;
| | - Abdul Mujib
- Cellular Differentiation and Molecular Genetics Section, Department of Botany, Jamia Hamdard, New Delhi 110062, India;
| | - Mehpara Maqsood
- Department of Botany, Government College for Women, M.A. Road, Srinagar 190001, India;
| | - Mir Khusrau
- Department of Botany, Government Degree College (Boys), Anantnag 231213, India;
| | - Ali Alsughayyir
- Department of Plant and Soil Sciences, Mississippi State University, 75 B.S. Hood Rd, Starkville, MS 39762, USA;
| | - Yaser Hassan Dewir
- Plant Production Department, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia;
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16
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Zhao W, Zheng XD, Tang PYZ, Li HM, Liu X, Zhong JJ, Tang YJ. Advances of antitumor drug discovery in traditional Chinese medicine and natural active products by using multi-active components combination. Med Res Rev 2023; 43:1778-1808. [PMID: 37183170 DOI: 10.1002/med.21963] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 03/03/2023] [Accepted: 04/12/2023] [Indexed: 05/16/2023]
Abstract
The antitumor efficacy of Chinese herbal medicines has been widely recognized. Leading compounds such as sterols, glycosides, flavonoids, alkaloids, terpenoids, phenylpropanoids, and polyketides constitute their complex active components. The antitumor monomers derived from Chinese medicine possess an attractive anticancer activity. However, their use was limited by low bioavailability, significant toxicity, and side effects, hindering their clinical applications. Recently, new chemical entities have been designed and synthesized by combining natural drugs with other small drug molecules or active moieties to improve the antitumor activity and selectivity, and reduce side effects. Such a novel conjugated drug that can interact with several vital biological targets in cells may have a more significant or synergistic anticancer activity than a single-molecule drug. In addition, antitumor conjugates could be obtained by combining pharmacophores containing two or more known drugs or leading compounds. Based on these studies, the new drug research and development could be greatly shortened. This study reviews the research progress of conjugates with antitumor activity based on Chinese herbal medicine. It is expected to serve as a valuable reference to antitumor drug research and clinical application of traditional Chinese medicine.
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Affiliation(s)
- Wei Zhao
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
| | - Xiao-Di Zheng
- Hubei Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, China
| | | | - Hong-Mei Li
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
| | - Xue Liu
- Jinan Intellectual Property Protection Center, Jinan, China
| | - Jian-Jiang Zhong
- State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Ya-Jie Tang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
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Al-Otaibi JS, Mary YS, Mary YS, Thomas R. Evidences of noncovalent interactions between indole and dichloromethane under different solvent conditions. J Mol Model 2023; 29:246. [PMID: 37442832 DOI: 10.1007/s00894-023-05623-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 06/14/2023] [Indexed: 07/15/2023]
Abstract
CONTEXT Theoretical investigation of indole (IND) and its binary combination with dichloromethane (DC) in various solvents were computed to track the impact of molecular interactions on spectral characteristics. When transitioning from plain drug to complexes, different modes of IND display a substantial shift in peak location. The 3561.26 cm-1 band shows (~15.58 cm-1) red shift upon dilution. The geometry in various solvents was calculated using quantum chemical calculation utilizing density functional theory (DFT). The highest ALIE values are located at the indole skeleton and on complexation with DC, and the ring atoms become more electron rich. The atom-centered density matrix propagation (ADMP) molecular dynamic (MD) calculation shows that the geometries optimized through the DFT calculation match the global minima effectively. MD simulations indicate that indole is more stable in water and methanol. METHODS DFT studies have been employed to study the interaction between indole and dichloromethane. CAM-B3LYP/6-311++G(d)(6D,7F) level of theory was employed using Gaussian 16 W suite. Quantum topological descriptors were discussed using quantum theory of atoms in molecules (QTAIM) with the help of Multiwfn software. Reduced density gradient (RDG) plot describes the nature of the interaction, while average local ionization energy (ALIE) explained the variation in local ionization energy of the molecular surface before and after complexation.
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Affiliation(s)
- Jamelah S Al-Otaibi
- Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
| | | | | | - Renjith Thomas
- Department of Chemistry, St. Berchmans College (Autonomous), Mahatma Gandhi University, Changanassery, Kerala, India
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Russo E, Grondona C, Brullo C, Spallarossa A, Villa C, Tasso B. Indole Antitumor Agents in Nanotechnology Formulations: An Overview. Pharmaceutics 2023; 15:1815. [PMID: 37514002 PMCID: PMC10385756 DOI: 10.3390/pharmaceutics15071815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/19/2023] [Accepted: 06/22/2023] [Indexed: 07/30/2023] Open
Abstract
The indole heterocycle represents one of the most important scaffolds in medicinal chemistry and is shared among a number of drugs clinically used in different therapeutic areas. Due to its varied biological activities, high unique chemical properties and significant pharmacological behaviors, indole derivatives have drawn considerable interest in the last decade as antitumor agents active against different types of cancers. The research of novel antiproliferative drugs endowed with enhanced efficacy and reduced toxicity led to the approval by U.S. Food and Drug Administration of the indole-based anticancer agents Sunitinib, Nintedanib, Osimertinib, Panobinostat, Alectinib and Anlotinib. Additionally, new drug delivery systems have been developed to protect the active principle from degradation and to direct the drug to the specific site for clinical use, thus reducing its toxicity. In the present work is an updated review of the recently approved indole-based anti-cancer agents and the nanotechnology systems developed for their delivery.
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Affiliation(s)
- Eleonora Russo
- Section of Medicinal and Cosmetic Chemistry, Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy
| | - Carola Grondona
- Section of Medicinal and Cosmetic Chemistry, Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy
| | - Chiara Brullo
- Section of Medicinal and Cosmetic Chemistry, Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy
| | - Andrea Spallarossa
- Section of Medicinal and Cosmetic Chemistry, Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy
| | - Carla Villa
- Section of Medicinal and Cosmetic Chemistry, Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy
| | - Bruno Tasso
- Section of Medicinal and Cosmetic Chemistry, Department of Pharmacy, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy
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Kornicka A, Gzella K, Garbacz K, Jarosiewicz M, Gdaniec M, Fedorowicz J, Balewski Ł, Kokoszka J, Ordyszewska A. Indole-Acrylonitrile Derivatives as Potential Antitumor and Antimicrobial Agents-Synthesis, In Vitro and In Silico Studies. Pharmaceuticals (Basel) 2023; 16:918. [PMID: 37513830 PMCID: PMC10386429 DOI: 10.3390/ph16070918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 07/30/2023] Open
Abstract
A series of 2-(1H-indol-2-yl)-3-acrylonitrile derivatives, 2a-x, 3, 4a-b, 5a-d, 6a-b, and 7, were synthesized as potential antitumor and antimicrobial agents. The structures of the prepared compounds were evaluated based on elemental analysis, IR, 1H- and 13NMR, as well as MS spectra. X-ray crystal analysis of the representative 2-(1H-indol-2-yl)-3-acrylonitrile 2l showed that the acrylonitrile double bond was Z-configured. All compounds were screened at the National Cancer Institute (USA) for their activities against a panel of approximately 60 human tumor cell lines and the relationship between structure and in vitro antitumor activity is discussed. Compounds of interest 2l and 5a-d showed significant growth inhibition potency against various tumor cell lines with the mean midpoint GI50 values of all tests in the range of 0.38-7.91 μM. The prominent compound with remarkable activity (GI50 = 0.0244-5.06 μM) and high potency (TGI = 0.0866-0.938 μM) against some cell lines of leukemia (HL-60(TB)), non-small cell lung cancer (NCI-H522), colon cancer (COLO 205), CNS cancer (SF-539, SNB-75), ovarian cancer ((OVCAR-3), renal cancer (A498, RXF 393), and breast cancer (MDA-MB-468) was 3-[4-(dimethylamino)phenyl]-2-(1-methyl-1H-indol-2-yl)acrylonitrile (5c). Moreover, the selected 2-(1H-indol-2-yl)-3-acrylonitriles 2a-c and 2e-x were evaluated for their antibacterial and antifungal activities against Gram-positive and Gram-negative pathogens as well as Candida albicans. Among them, 2-(1H-indol-2-yl)-3-(1H-pyrrol-2-yl)acrylonitrile (2x) showed the most potent antimicrobial activity and therefore it can be considered as a lead structure for further development of antimicrobial agents. Finally, molecular docking studies as well as drug-likeness and ADME profile prediction were carried out.
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Affiliation(s)
- Anita Kornicka
- Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
| | - Karol Gzella
- Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
| | - Katarzyna Garbacz
- Department of Oral Microbiology, Medical Faculty, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Małgorzata Jarosiewicz
- Department of Oral Microbiology, Medical Faculty, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Maria Gdaniec
- Faculty of Chemistry, Adam Mickiewicz University, 61-614 Poznań, Poland
| | - Joanna Fedorowicz
- Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
| | - Łukasz Balewski
- Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
| | - Jakub Kokoszka
- Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
| | - Anna Ordyszewska
- Department of Inorganic Chemistry, Faculty of Chemistry and Advanced Materials Centers, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland
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Hazarika S, Borah P, Deb PK, Venugopala KN, Hemalatha S. Icacinaceae Plant Family: A Recapitulation of the Ethnobotanical, Phytochemical, Pharmacological, and Biotechnological Aspects. Curr Pharm Des 2023; 29:1193-1217. [PMID: 37132105 DOI: 10.2174/1381612829666230502164605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 03/05/2023] [Accepted: 03/06/2023] [Indexed: 05/04/2023]
Abstract
Icacinaceae, an Angiospermic family comprising 35 genera and 212 accepted species, including trees, shrubs, and lianas with pantropical distribution, is one of the most outshining yet least explored plant families, which despite its vital role as a source of pharmaceuticals and nutraceuticals has received a meagre amount of attraction from the scientific community. Interestingly, Icacinaceae is considered a potential alternative resource for camptothecin and its derivatives, which are used in treating ovarian and metastatic colorectal cancer. However, the concept of this family has been revised many times, but further recognition is still needed. The prime objective of this review is to compile the available information on this family in order to popularize it in the scientific community and the general population and promote extensive exploration of these taxa. The phytochemical preparations or isolated compounds from the Icacinaceae family have been centrally amalgamated to draw diverse future prospects from this inclusive plant species. The ethnopharmacological activities and the associated endophytes and cell culture techniques are also depicted. Nevertheless, the methodical evaluation of the Icacinaceae family is the only means to preserve and corroborate the folkloristic remedial effects and provide scientific recognition of its potencies before they are lost under the blanket of modernization.
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Affiliation(s)
- Sangeeta Hazarika
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, Uttar Pradesh, India
| | - Pobitra Borah
- School of Pharmacy, Graphic Era Hill University, Dehradun, 248002, Uttarakhand, India
| | - Pran Kishore Deb
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, PO Box 1, Amman, 19392, Jordan
| | - Katharigatta N Venugopala
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, Kingdom of Saudi Arabia
- Department of Biotechnology and Food Science, Durban University of Technology, Durban, 4001, South Africa
| | - Siva Hemalatha
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, Uttar Pradesh, India
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21
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Milne N, Sáez-Sáez J, Nielsen AM, Dyekjaer JD, Rago D, Kristensen M, Wulff T, Borodina I. Engineering Saccharomyces cerevisiae for the de novo Production of Halogenated Tryptophan and Tryptamine Derivatives. ChemistryOpen 2023; 12:e202200266. [PMID: 36929157 PMCID: PMC10068768 DOI: 10.1002/open.202200266] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/28/2023] [Indexed: 03/18/2023] Open
Abstract
The indole scaffold is a recurring structure in multiple bioactive heterocycles and natural products. Substituted indoles like the amino acid tryptophan serve as a precursor for a wide range of natural products with pharmaceutical or agrochemical applications. Inspired by the versatility of these compounds, medicinal chemists have for decades exploited indole as a core structure in the drug discovery process. With the aim of tuning the properties of lead drug candidates, regioselective halogenation of the indole scaffold is a common strategy. However, chemical halogenation is generally expensive, has a poor atom economy, lacks regioselectivity, and generates hazardous waste streams. As an alternative, in this work we engineer the industrial workhorse Saccharomyces cerevisiae for the de novo production of halogenated tryptophan and tryptamine derivatives. Functional expression of bacterial tryptophan halogenases together with a partner flavin reductase and a tryptophan decarboxylase resulted in the production of halogenated tryptophan and tryptamine with chlorine or bromine. Furthermore, by combining tryptophan halogenases, production of di-halogenated molecules was also achieved. Overall, this works paves the road for the production of new-to-nature halogenated natural products in yeast.
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Affiliation(s)
- Nicholas Milne
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark.,Octarine Bio ApS, Lersø Parkallé 42, 1. Sal, 2100, Copenhagen, Denmark
| | - Javier Sáez-Sáez
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark
| | - Annette Munch Nielsen
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark.,Octarine Bio ApS, Lersø Parkallé 42, 1. Sal, 2100, Copenhagen, Denmark
| | - Jane Dannow Dyekjaer
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark
| | - Daniela Rago
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark
| | - Mette Kristensen
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark
| | - Tune Wulff
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark
| | - Irina Borodina
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark
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22
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Raorane ML, Manz C, Hildebrandt S, Mielke M, Thieme M, Keller J, Bunzel M, Nick P. Cell type matters: competence for alkaloid metabolism differs in two seed-derived cell strains of Catharanthus roseus. PROTOPLASMA 2023; 260:349-369. [PMID: 35697946 PMCID: PMC9931846 DOI: 10.1007/s00709-022-01781-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 05/31/2022] [Indexed: 06/15/2023]
Abstract
Since the discovery of the anticancer drugs vinblastine and vincristine, Catharanthus roseus has been intensively studied for biosynthesis of several terpene indole alkaloids (TIAs). Due to their low abundance in plant tissues at a simultaneously high demand, modes of production alternative to conventional extraction are mandatory. Plant cell fermentation might become one of these alternatives, yet decades of research have shown limited success to certain product classes, leading to the question: how to preserve the intrinsic ability to produce TIAs (metabolic competence) in cell culture? We used the strategy to use the developmental potency of mature embryos to generate such strains. Two cell strains (C1and C4) from seed embryos of Catharanthus roseus were found to differ not only morphologically, but also in their metabolic competence. This differential competence became manifest not only under phytohormone elicitation, but also upon feeding with alkaloid pathway precursors. The more active strain C4 formed larger cell aggregates and was endowed with longer mitochondria. These cellular features were accompanied by higher alkaloid accumulation in response to methyl jasmonate (MeJA) elicitation. The levels of catharanthine could be increased significantly, while the concurrent vindoline branch of the pathway was blocked, such that no bisindole alkaloids were detectable. By feeding vindoline to MeJA-elicited C4 cells, vincristine became detectable; however, only to marginal amounts. In conclusion, these results show that cultured cells are not "de-differentiated", but can differ in metabolic competence. In addition to elicitation and precursor feeding, the cellular properties of the "biomatter" are highly relevant for the success of plant cell fermentation.
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Affiliation(s)
- Manish L Raorane
- Botanical Institute, Karlsruhe Institute of Technology, Fritz-Haber-Weg 4, 76131, Karlsruhe, Germany.
- Institute of Pharmacy, Martin-Luther-University, Hoher Weg 8, 06120, Halle-WittenbergHalle (Saale), Germany.
| | - Christina Manz
- Botanical Institute, Karlsruhe Institute of Technology, Fritz-Haber-Weg 4, 76131, Karlsruhe, Germany
| | - Sarah Hildebrandt
- Botanical Institute, Karlsruhe Institute of Technology, Fritz-Haber-Weg 4, 76131, Karlsruhe, Germany
| | - Marion Mielke
- Botanical Institute, Karlsruhe Institute of Technology, Fritz-Haber-Weg 4, 76131, Karlsruhe, Germany
| | - Marc Thieme
- Botanical Institute, Karlsruhe Institute of Technology, Fritz-Haber-Weg 4, 76131, Karlsruhe, Germany
| | - Judith Keller
- Institute of Applied Biosciences, Department of Food Chemistry and Phytochemistry, Karlsruhe Institute of Technology (KIT), 76131, Karlsruhe, Germany
| | - Mirko Bunzel
- Institute of Applied Biosciences, Department of Food Chemistry and Phytochemistry, Karlsruhe Institute of Technology (KIT), 76131, Karlsruhe, Germany
| | - Peter Nick
- Botanical Institute, Karlsruhe Institute of Technology, Fritz-Haber-Weg 4, 76131, Karlsruhe, Germany
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23
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Rao MRP, Ghadge I, Kulkarni S, R. Madgulkar A. Importance of Plant Secondary Metabolites in Modern Therapy. REFERENCE SERIES IN PHYTOCHEMISTRY 2023:1-31. [DOI: 10.1007/978-3-031-30037-0_5-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 07/26/2023] [Indexed: 01/05/2025]
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24
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Veeramohan R, Zamani AI, Azizan KA, Goh HH, Aizat WM, Razak MFA, Yusof NSM, Mansor SM, Baharum SN, Ng CL. Comparative metabolomics analysis reveals alkaloid repertoires in young and mature Mitragyna speciosa (Korth.) Havil. Leaves. PLoS One 2023; 18:e0283147. [PMID: 36943850 PMCID: PMC10030037 DOI: 10.1371/journal.pone.0283147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 03/02/2023] [Indexed: 03/23/2023] Open
Abstract
The fresh leaves of Mitragyna speciosa (Korth.) Havil. have been traditionally consumed for centuries in Southeast Asia for its healing properties. Although the alkaloids of M. speciosa have been studied since the 1920s, comparative and systematic studies of metabolite composition based on different leaf maturity levels are still lacking. This study assessed the secondary metabolite composition in two different leaf stages (young and mature) of M. speciosa, using an untargeted liquid chromatography-electrospray ionisation-time-of-flight-mass spectrometry (LC-ESI-TOF-MS) metabolite profiling. The results revealed 86 putatively annotated metabolite features (RT:m/z value) comprising 63 alkaloids, 10 flavonoids, 6 terpenoids, 3 phenylpropanoids, and 1 of each carboxylic acid, glucoside, phenol, and phenolic aldehyde. The alkaloid features were further categorised into 14 subclasses, i.e., the most abundant class of secondary metabolites identified. As per previous reports, indole alkaloids are the most abundant alkaloid subclass in M. speciosa. The result of multivariate analysis (MVA) using principal component analysis (PCA) showed a clear separation of 92.8% between the young and mature leaf samples, indicating a high variance in metabolite levels between them. Akuammidine, alstonine, tryptamine, and yohimbine were tentatively identified among the many new alkaloids reported in this study, depicting the diverse biological activities of M. speciosa. Besides delving into the knowledge of metabolite distribution in different leaf stages, these findings have extended the current alkaloid repository of M. speciosa for a better understanding of its pharmaceutical potential.
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Affiliation(s)
- Rubashiny Veeramohan
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia
| | - Arief Izzairy Zamani
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia
- Leave a Nest Malaysia Sdn Bhd, Cyberjaya, Selangor, Malaysia
| | - Kamalrul Azlan Azizan
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia
| | - Hoe-Han Goh
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia
| | - Wan Mohd Aizat
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia
| | - Mohd Fauzi Abd Razak
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia
| | | | | | | | - Chyan Leong Ng
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia
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25
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Sunitha Boda, Nukala SK, Manchal R. Synthesis of Some New Indole-1,3,4-Oxadiazole Hybrids as Tubulin Polymerization Inhibitors. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2022. [DOI: 10.1134/s1068162023010077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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26
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Ahmed MB, Islam SU, Alghamdi AAA, Kamran M, Ahsan H, Lee YS. Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation. Int J Mol Sci 2022; 23:15765. [PMID: 36555406 PMCID: PMC9779495 DOI: 10.3390/ijms232415765] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/02/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthetic and natural chemicals are effective for cancer chemoprevention, i.e., the use of exogenous medicine to inhibit or impede tumor development. They help regulate molecular pathways linked to the development and spread of cancer. They can enhance antioxidant status, inactivating carcinogens, suppressing proliferation, inducing cell cycle arrest and death, and regulating the immune system. While focusing on four main categories of plant-based anticancer agents, i.e., epipodophyllotoxin, camptothecin derivatives, taxane diterpenoids, and vinca alkaloids and their mode of action, we review the anticancer effects of phytochemicals, like quercetin, curcumin, piperine, epigallocatechin gallate (EGCG), and gingerol. We examine the different signaling pathways associated with cancer and how inflammation as a key mechanism is linked to cancer growth.
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Affiliation(s)
- Muhammad Bilal Ahmed
- BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Salman Ul Islam
- Department of Pharmacy, Cecos University, Peshawar, Street 1, Sector F 5 Phase 6 Hayatabad, Peshawar 25000, Pakistan
| | | | - Muhammad Kamran
- School of Molecular Sciences, The University of Western Australia, M310, 35 Stirling Hwy, Perth, WA 6009, Australia
| | - Haseeb Ahsan
- Department of Pharmacy, Faculty of Life and Environmental Sciences, University of Peshawar, Peshawar 25120, Pakistan
| | - Young Sup Lee
- BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
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27
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Hari Gangadhar K, Benarjee V, Ratnamala A. Synthesis of 4‐Azaindole‐morpholine‐1,3,4‐oxadiazole Conjugates as Epidermal Growth Factor Receptor Inhibitors. ChemistrySelect 2022. [DOI: 10.1002/slct.202202593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
| | - Velaga Benarjee
- Department of Inorganic and Analytical Chemistry Andhra University Visakhapatnam, Andhra Pradesh India
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28
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Synthesis of indole-tetrazole coupled aromatic amides; In vitro anticancer activity, in vitro tubulin polymerization inhibition assay and in silico studies. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.133556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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29
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Ahmadzadeh M, Keshtkar AH, Moslemkhany K, Ahmadzadeh M. Effect of the plant probiotic bacteria on terpenoid indole alkaloid biosynthesis pathway gene expression profiling, vinblastine and vincristine content in the root of Catharanthus roseus. Mol Biol Rep 2022; 49:10357-10365. [PMID: 36097118 DOI: 10.1007/s11033-022-07841-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 07/30/2022] [Accepted: 08/04/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND Catharanthus roseus is the sole resource of vinblastine and vincristine, two TIAs of great interest for their powerful anticancer activities. Increasing the concentration of these alkaloids in various organs of the plant is one of the important goals in C. roseus breeding programs. Plant probiotic bacteria (PBB) act as biotic elicitors and can induce the synthesis of secondary products in plants. The purpose of this research is to study the effects of PBB on expression of the TIA biosynthetic pathway genes and the content of alkaloids in C. roseus. METHODS AND RESULTS The individual and combined effects of P. fluorescens strains 169 and A. brasilense strains Ab-101 was studied for expression of the TIA biosynthetic pathway genes (G10H, DAT, T16H and CrPRX) using qRT-PCR and the content of vinblastine and vincristine using HPLC method in roots of C. roseus. P. fluorescens. This drastically increased the content of vinblastine and vincristine alkaloids, compared to the control in the roots, to 174 and 589 (µg/g), respectively. Molecular analysis showed bacterium significantly increased the expression of more genes in the TIA biosynthetic pathway compared to the control. P. fluorescens increased the expression of the final gene of the biosynthetic pathway (CrPRX) 47.9 times compared to the control. Our findings indicate the correlation between transcriptional and metabolic outcomes. The same was true for A. brasilense. CONCLUSIONS It can be concluded that seed treatments and seedling root treatments composed of naturally occurring probiotic bacteria are likely to be widely applicable for inducing enhanced alkaloid contents in medicinal plants.
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Affiliation(s)
- M Ahmadzadeh
- Faculty of Agriculture, Buali Sina University, Hamedan, Iran
| | - A H Keshtkar
- Faculty of Agriculture, Buali Sina University, Hamedan, Iran.
| | - K Moslemkhany
- Seed and Plant Certification and Registration Institute, Agricultural Research, Education and Extension Organisation (AREEO), Tehran, Iran
| | - M Ahmadzadeh
- College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
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30
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Morey KJ, Peebles CAM. Hairy roots: An untapped potential for production of plant products. FRONTIERS IN PLANT SCIENCE 2022; 13:937095. [PMID: 35991443 PMCID: PMC9389236 DOI: 10.3389/fpls.2022.937095] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 07/18/2022] [Indexed: 06/15/2023]
Abstract
While plants are an abundant source of valuable natural products, it is often challenging to produce those products for commercial application. Often organic synthesis is too expensive for a viable commercial product and the biosynthetic pathways are often so complex that transferring them to a microorganism is not trivial or feasible. For plants not suited to agricultural production of natural products, hairy root cultures offer an attractive option for a production platform which offers genetic and biochemical stability, fast growth, and a hormone free culture media. Advances in metabolic engineering and synthetic biology tools to engineer hairy roots along with bioreactor technology is to a point where commercial application of the technology will soon be realized. We discuss different applications of hairy roots. We also use a case study of the advancements in understanding of the terpenoid indole alkaloid pathway in Catharanthus roseus hairy roots to illustrate the advancements and challenges in pathway discovery and in pathway engineering.
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31
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Emodin Sensitizes Cervical Cancer Cells to Vinblastine by Inducing Apoptosis and Mitotic Death. Int J Mol Sci 2022; 23:ijms23158510. [PMID: 35955645 PMCID: PMC9369386 DOI: 10.3390/ijms23158510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/28/2022] [Accepted: 07/28/2022] [Indexed: 12/10/2022] Open
Abstract
In recent years, studies on the effects of combining novel plant compounds with cytostatics used in cancer therapy have received considerable attention. Since emodin sensitizes tumor cells to chemotherapeutics, we evaluated changes in cervical cancer cells after its combination with the antimitotic drug vinblastine. Cellular changes were demonstrated using optical, fluorescence, confocal and electron microscopy. Cell viability was assessed by MTT assay. The level of apoptosis, caspase 3/7, Bcl-2 protein, ROS, mitochondrial membrane depolarization, cell cycle and degree of DNA damage were analyzed by flow cytometry. The microscopic image showed indicators characteristic for emodin- and vinblastine-induced mitotic catastrophe, i.e., multinucleated cells, giant cells, cells with micronuclei, and abnormal mitotic figures. These compounds also increased blocking of cells in the G2/M phase, and the generated ROS induced swelling and mitochondrial damage. This translated into the growth of apoptotic cells with active caspase 3/7 and inactivation of Bcl-2 protein and active ATM kinase. Emodin potentiated the cytotoxic effect of vinblastine, increasing oxidative stress, mitotic catastrophe and apoptosis. Preliminary studies show that the combined action of both compounds, may constitute an interesting form of anticancer therapy.
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32
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Dhyani P, Quispe C, Sharma E, Bahukhandi A, Sati P, Attri DC, Szopa A, Sharifi-Rad J, Docea AO, Mardare I, Calina D, Cho WC. Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell Int 2022; 22:206. [PMID: 35655306 PMCID: PMC9161525 DOI: 10.1186/s12935-022-02624-9] [Citation(s) in RCA: 168] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 05/25/2022] [Indexed: 01/09/2023] Open
Abstract
Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and drug therapy, along with others, which not only put a tremendous economic effect on patients but also develop drug resistance in patients with time. A significant number of cancer cases can be prevented/treated by implementing evidence-based preventive strategies. Plant-based drugs have evolved as promising preventive chemo options both in developing and developed nations. The secondary plant metabolites such as alkaloids have proven efficacy and acceptability for cancer treatment. Apropos, this review deals with a spectrum of promising alkaloids such as colchicine, vinblastine, vincristine, vindesine, vinorelbine, and vincamine within different domains of comprehensive information on these molecules such as their medical applications (contemporary/traditional), mechanism of antitumor action, and potential scale-up biotechnological studies on an in-vitro scale. The comprehensive information provided in the review will be a valuable resource to develop an effective, affordable, and cost effective cancer management program using these alkaloids.
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Affiliation(s)
- Praveen Dhyani
- Department of Biotechnology, Kumaun University, Bhimtal, Uttarakhand 263 136 India
| | - Cristina Quispe
- Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, 1110939 Iquique, Chile
| | - Eshita Sharma
- Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, Punjab 143 005 India
| | - Amit Bahukhandi
- G.B. Pant National Institute of Himalayan Environment, Kosi-Katarmal, Almora, Uttarakhand 263 643 India
| | - Priyanka Sati
- Graphic Era University, Dehradun, Uttarakhand 248 001 India
| | - Dharam Chand Attri
- G.B. Pant National Institute of Himalayan Environment, Kosi-Katarmal, Almora, Uttarakhand 263 643 India
| | - Agnieszka Szopa
- Chair and Department of Pharmaceutical Botany, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland
| | | | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ileana Mardare
- Department of Public Health and Management, Carol Davila University of Medicine and Pharmacy Bucharest, 050463 Bucharest, Romania
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong People’s Republic of China
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Mazumder K, Aktar A, Roy P, Biswas B, Hossain ME, Sarkar KK, Bachar SC, Ahmed F, Monjur-Al-Hossain ASM, Fukase K. A Review on Mechanistic Insight of Plant Derived Anticancer Bioactive Phytocompounds and Their Structure Activity Relationship. Molecules 2022; 27:3036. [PMID: 35566385 PMCID: PMC9102595 DOI: 10.3390/molecules27093036] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 11/16/2022] Open
Abstract
Cancer is a disorder that rigorously affects the human population worldwide. There is a steady demand for new remedies to both treat and prevent this life-threatening sickness due to toxicities, drug resistance and therapeutic failures in current conventional therapies. Researchers around the world are drawing their attention towards compounds of natural origin. For decades, human beings have been using the flora of the world as a source of cancer chemotherapeutic agents. Currently, clinically approved anticancer compounds are vincristine, vinblastine, taxanes, and podophyllotoxin, all of which come from natural sources. With the triumph of these compounds that have been developed into staple drug products for most cancer therapies, new technologies are now appearing to search for novel biomolecules with anticancer activities. Ellipticine, camptothecin, combretastatin, curcumin, homoharringtonine and others are plant derived bioactive phytocompounds with potential anticancer properties. Researchers have improved the field further through the use of advanced analytical chemistry and computational tools of analysis. The investigation of new strategies for administration such as nanotechnology may enable the development of the phytocompounds as drug products. These technologies have enhanced the anticancer potential of plant-derived drugs with the aim of site-directed drug delivery, enhanced bioavailability, and reduced toxicity. This review discusses mechanistic insights into anticancer compounds of natural origins and their structural activity relationships that make them targets for anticancer treatments.
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Affiliation(s)
- Kishor Mazumder
- Department of Pharmacy, Jashore University of Science and Technology, Jashore 7408, Bangladesh; (A.A.); (P.R.); (B.B.); (M.E.H.); (K.K.S.)
- School of Optometry and Vision Science, UNSW Medicine, University of New South Wales (UNSW), Sydney, NSW 2052, Australia
| | - Asma Aktar
- Department of Pharmacy, Jashore University of Science and Technology, Jashore 7408, Bangladesh; (A.A.); (P.R.); (B.B.); (M.E.H.); (K.K.S.)
| | - Priyanka Roy
- Department of Pharmacy, Jashore University of Science and Technology, Jashore 7408, Bangladesh; (A.A.); (P.R.); (B.B.); (M.E.H.); (K.K.S.)
| | - Biswajit Biswas
- Department of Pharmacy, Jashore University of Science and Technology, Jashore 7408, Bangladesh; (A.A.); (P.R.); (B.B.); (M.E.H.); (K.K.S.)
| | - Md. Emran Hossain
- Department of Pharmacy, Jashore University of Science and Technology, Jashore 7408, Bangladesh; (A.A.); (P.R.); (B.B.); (M.E.H.); (K.K.S.)
| | - Kishore Kumar Sarkar
- Department of Pharmacy, Jashore University of Science and Technology, Jashore 7408, Bangladesh; (A.A.); (P.R.); (B.B.); (M.E.H.); (K.K.S.)
| | - Sitesh Chandra Bachar
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1207, Bangladesh; (S.C.B.); (F.A.)
| | - Firoj Ahmed
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1207, Bangladesh; (S.C.B.); (F.A.)
| | - A. S. M. Monjur-Al-Hossain
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka 1207, Bangladesh;
| | - Koichi Fukase
- Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
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Liu H, Panjikar S, Sheng X, Futamura Y, Zhang C, Shao N, Osada H, Zou H. β-Methyltryptamine Provoking the Crucial Role of Strictosidine Synthase Tyr151-OH for Its Stereoselective Pictet-Spengler Reactions to Tryptoline-type Alkaloids. ACS Chem Biol 2022; 17:187-197. [PMID: 34994203 DOI: 10.1021/acschembio.1c00844] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Strictosidine synthase (STR), the gate enzyme for monoterpenoid indole alkaloid biosynthesis, catalyzes the Pictet-Spengler reaction (PSR) of various tryptamine derivatives with secologanin assisted by "indole sandwich" stabilization. Continuous exploration with β-methyltryptamine (IPA) stereoselectively delivered the C6-methylstrictosidines and C6-methylvincosides by enzymatic and nonenzymatic PSR, respectively. Unexpectedly, the first "nonindole sandwich" binding mode was witnessed by the X-ray structures of STR1-ligand complexes. Site-directed mutagenesis revealed the critical cryptic role of the hydroxyl group of Tyr151 in IPA biotransformation. Further computational calculations demonstrated the adjustable IPA position in STR1 upon the binding of secologanin, and Tyr151-OH facilitates the productive PSR binding mode via an advantageous hydrogen-bond network. Further chemo-enzymatic manipulation of C6-methylvincosides successfully resulted in the discovered antimalarial framework (IC50 = 0.92 μM).
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Affiliation(s)
- Haicheng Liu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. China
| | - Santosh Panjikar
- Australia & Department of Molecular Biology and Biochemistry, Monash University, ANSTO, Australian Synchrotron, 800 Blackburn Road, Victoria 3168, Australia
| | - Xiang Sheng
- Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, & National Technology Innovation Center for Synthetic Biology, Tianjin 300308, China
| | - Yushi Futamura
- Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
| | - Chenghua Zhang
- Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, & National Technology Innovation Center for Synthetic Biology, Tianjin 300308, China
- School of Basic Medical Sciences, North Sichuan Medical College, No. 55 Dongshun Road, Gaoping District, Nanchong 637000, China
| | - Nana Shao
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. China
| | - Hiroyuki Osada
- Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
| | - Hongbin Zou
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. China
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Mondal D, Amin SA, Moinul M, Das K, Jha T, Gayen S. How the structural properties of the indole derivatives are important in kinase targeted drug design?: A case study on tyrosine kinase inhibitors. Bioorg Med Chem 2022; 53:116534. [PMID: 34864496 DOI: 10.1016/j.bmc.2021.116534] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/18/2022]
Abstract
Kinases are considered as important signalling enzymes that illustrate 20% of the druggable genome. Human kinase family comprises >500 protein kinases and about 20 lipid kinases. Protein kinases are responsible for the mechanism of protein phosphorylation. These are necessary for regulation of various cellular activities including proliferation, cell cycle, apoptosis, motility, growth, differentiation, etc. Their deregulation leads to disruption of many cellular processes leading to different diseases most importantly cancer. Thus, kinases are considered as valuable targets in different types of cancer as well as other diseases. Researchers around the world are actively engaged in developing inhibitors based on distinct chemical scaffolds. Indole represents as a versatile scaffold in the naturally occurring and bioactive molecules. It is also used as a privileged scaffold for the target-based drug design against different diseases. This present article aim to review the applications of indole scaffold in the design of inhibitors against different tyrosine kinases such as epidermal growth factor receptors (EGFRs), vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), etc. Important structure activity relationships (SARs) of indole derivatives were discussed. The present work is an attempt to summarize all the crucial structural information which is essential for the development of indole based tyrosine kinase inhibitors with improved potency.
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Affiliation(s)
- Dipayan Mondal
- Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar 470003, MP, India
| | - Sk Abdul Amin
- Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, P. O. Box 17020, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
| | - Md Moinul
- Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
| | - Kalpataru Das
- Advanced Organic Synthesis Laboratory, Department of Chemistry, Dr. Harisingh Gour University, Sagar 470003, MP, India
| | - Tarun Jha
- Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, P. O. Box 17020, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
| | - Shovanlal Gayen
- Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar 470003, MP, India; Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
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Kumar G, Du B, Chen J. Effects and mechanisms of dietary bioactive compounds on breast cancer prevention. Pharmacol Res 2021; 178:105974. [PMID: 34818569 DOI: 10.1016/j.phrs.2021.105974] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/05/2021] [Accepted: 11/06/2021] [Indexed: 12/17/2022]
Abstract
Breast cancer (BC) is the most often diagnosed cancer among females globally and has become an increasing global health issue over the last decades. Despite the substantial improvement in screening methods for initial diagnosis, effective therapy remains lacking. Still, there has been high recurrence and disease progression after treatment of surgery, endocrine therapy, chemotherapy, and radiotherapy. Considering this view, there is a crucial requirement to develop safe, freely accessible, and effective anticancer therapy for BC. The dietary bioactive compounds as auspicious anticancer agents have been recognized to be active and their implications in the treatment of BC with negligible side effects. Hence, this review focused on various dietary bioactive compounds as potential therapeutic agents in the prevention and treatment of BC with the mechanisms of action. Bioactive compounds have chemo-preventive properties as they inhibit the proliferation of cancer cells, downregulate the expression of estrogen receptors, and cell cycle arrest by inducing apoptotic settings in tumor cells. Therapeutic drugs or natural compounds generally incorporate engineered nanoparticles with ideal sizes, shapes, and enhance their solubility, circulatory half-life, and biodistribution. All data of in vitro, in vivo, and clinical studies of dietary bioactive compounds and their impact on BC were collected from Science Direct, PubMed, and Google Scholar. The data of chemopreventive and anticancer activity of dietary bioactive compounds were collected and orchestrated in a suitable place in the review. These shreds of data will be extremely beneficial to recognize a series of additional diet-derived bioactive compounds to treat BC with the lowest side effects.
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Affiliation(s)
- Ganesan Kumar
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Bing Du
- College of Food Science, South China Agricultural University, Guangzhou, Guangdong 510640, China
| | - Jianping Chen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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Birat K, Siddiqi TO, Mir SR, Aslan J, Bansal R, Khan W, Dewangan RP, Panda BP. Enhancement of vincristine under in vitro culture of Catharanthus roseus supplemented with Alternaria sesami endophytic fungal extract as a biotic elicitor. Int Microbiol 2021; 25:275-284. [PMID: 34622356 DOI: 10.1007/s10123-021-00213-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/19/2021] [Accepted: 09/21/2021] [Indexed: 10/20/2022]
Abstract
Vincristine, one of the major vinca alkaloid of Catharanthus roseus (L.) G. Don. (Apocynaceae), was enhanced under in vitro callus culture of C. roseus using fungal extract of an endophyte Alternaria sesami isolated from the surface-sterilized root cuttings of C. roseus. Vindoline, a precursor molecule for vincristine production, was detected for the first time in the fungal endophyte A. sesami which was used as a biotic elicitor in this study to enhance vincristine content in the C. roseus callus. It was identified using high-performance liquid chromatography and mass spectroscopy techniques by matching retention time and mass data with reference molecule. Supplementing the heat sterilized A. sesami endophytic fungal culture extract into the callus culture medium of C. roseus resulted in the enhancement of vincristine content in C. roseus callus by 21.717% after 105-day culture.
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Affiliation(s)
- Kanchan Birat
- Microbial and Pharmaceutical Biotechnology Laboratory, Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India.,Molecular Ecology Laboratory, Department of Botany, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Tariq Omar Siddiqi
- Molecular Ecology Laboratory, Department of Botany, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Showkat Rasool Mir
- Phytopharmaceuticals Research Laboratory, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Junaid Aslan
- Microbial and Pharmaceutical Biotechnology Laboratory, Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Rakhi Bansal
- Microbial and Pharmaceutical Biotechnology Laboratory, Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Washim Khan
- Microbial and Pharmaceutical Biotechnology Laboratory, Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Rikeshwer Prasad Dewangan
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Bibhu Prasad Panda
- Microbial and Pharmaceutical Biotechnology Laboratory, Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India.
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Mitra S, Prova SR, Sultana SA, Das R, Nainu F, Emran TB, Tareq AM, Uddin MS, Alqahtani AM, Dhama K, Simal-Gandara J. Therapeutic potential of indole alkaloids in respiratory diseases: A comprehensive review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 90:153649. [PMID: 34325978 DOI: 10.1016/j.phymed.2021.153649] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 07/01/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Indole alkaloids are very promising for potential therapeutic purposes and appear to be particularly effective against respiratory diseases. Several experimental studies have been performed, both in vivo and in vitro, to evaluate the effectiveness of indole alkaloids for the management of respiratory disorders, including asthma, emphysema, tuberculosis, cancer, and pulmonary fibrosis. PURPOSE The fundamental objective of this review was to summarize the in-depth therapeutic potential of indole alkaloids against various respiratory disorders. STUDY DESIGN In addition to describing the therapeutic potential, this review also evaluates the toxicity of these alkaloids, which have been utilized for therapeutic benefits but have demonstrated toxic consequences. Some indole alkaloids, including scholaricine, 19-epischolaricine, vallesamine, and picrinine, which are derived from the plant Alstonia scholaris, have shown toxic effects in non-rodent models. METHODS This review also discusses clinical studies exploring the therapeutic efficacy of indole alkaloids, which have confirmed the promising benefits observed in vivo and in vitro. RESULTS The indole alkaloidal compounds have shown efficacy in subjects with respiratory diseases. CONCLUSION The available data established both preclinical and clinical studies confirm the potential of indole alkaloids to treat the respiratory disorders.
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Affiliation(s)
- Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Shajuthi Rahman Prova
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Sifat Ara Sultana
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Rajib Das
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Firzan Nainu
- Faculty of Pharmacy, Hasanuddin University, Makassar, South Sulawesi 90245, Indonesia
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh.
| | - Abu Montakim Tareq
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh
| | - Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka 1213, Bangladesh; Pharmakon Neuroscience Research Network, Dhaka 1207, Bangladesh
| | - Ali M Alqahtani
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E32004 Ourense, Spain.
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Synthesis of New Highly Functionalized 1 H-Indole-2-carbonitriles via Cross-Coupling Reactions. Molecules 2021; 26:molecules26175287. [PMID: 34500719 PMCID: PMC8434198 DOI: 10.3390/molecules26175287] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/26/2021] [Accepted: 08/27/2021] [Indexed: 11/29/2022] Open
Abstract
An approach for the preparation of polysubstituted indole-2-carbonitriles through a cross-coupling reaction of compounds 1-(but-2-ynyl)-1H-indole-2-carbonitriles and 1-benzyl-3-iodo-1H-indole-2-carbonitriles is described. The reactivity of indole derivatives with iodine at position 3 was studied using cross-coupling reactions. The Sonogashira, Suzuki–Miyaura, Stille and Heck cross-couplings afforded a variety of di-, tri- and tetra-substituted indole-2-carbonitriles.
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Patel A, Vanecha R, Patel J, Patel D, Shah U, Bambharoliya T. Development of Natural Bioactive Alkaloids: Anticancer perspective. Mini Rev Med Chem 2021; 22:200-212. [PMID: 34254913 DOI: 10.2174/1389557521666210712111331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 01/11/2021] [Accepted: 04/20/2021] [Indexed: 11/22/2022]
Abstract
Cancer is a frightful disease that still poses a 'nightmare' worldwide, causing millions of casualties annually due to one of the human race's most significant healthcare challenges that requires a pragmatic treatment strategy. However, plants and plant-derived products revolutionize the field as they are quick, cleaner, eco-friendly, low-cost, effective, and less toxic than conventional treatment methods. Plants are repositories for new chemical entities and have a promising cancer research path, supplying 60% of the anticancer agents currently used. Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery and development. However, some alkaloids derived from natural herbs display anti-proliferation and antimetastatic activity on different forms of cancer, both in vitro and in vivo. Alkaloids have also been widely formulated as anticancer medications, such as camptothecin and vinblastine. Still, more research and clinical trials are required before final recommendations can be made on specific alkaloids. This review focuses on the naturally-derived bioactive alkaloids with prospective anticancer properties based on the information in the literature.
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Affiliation(s)
- Ashish Patel
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa-388421, Anand, Gujarat, India
| | - Ravi Vanecha
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa-388421, Anand, Gujarat, India
| | - Jay Patel
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa-388421, Anand, Gujarat, India
| | - Divy Patel
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa-388421, Anand, Gujarat, India
| | - Umang Shah
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa-388421, Anand, Gujarat, India
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Design, synthesis and broad spectrum antibreast cancer activity of diarylindoles via induction of apoptosis in aggressive breast cancer cells. Bioorg Med Chem 2021; 42:116252. [PMID: 34153643 DOI: 10.1016/j.bmc.2021.116252] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/23/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023]
Abstract
Breast cancer is the second leading cause of cancer deaths in women with significant morbidity and mortality. Present study describes design, synthesis and detailed pharmacology of indole derivatives exhibiting remarkable broad spectrum antiproliferative activity against breast cancer cells. Detailed mechanistic evaluations confirmed induction of G0/G1 arrest, apoptosis induction, loss of mitochondrial integrity, enhanced ROS generation, autophagy, estrogen receptor β-transactivation and increased tubulin polymerization. In in-vivo efficacy studies in rodent model, these indole derivatives induced significant regression in mice mammary tumour on 21 days daily oral dose. Moreover, compounds 19 and 23 were safe in Swiss albino mice in safety studies. These diarylindoles may further be optimized for better efficacy.
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The Phytochemical Analysis of Vinca L. Species Leaf Extracts Is Correlated with the Antioxidant, Antibacterial, and Antitumor Effects. Molecules 2021; 26:molecules26103040. [PMID: 34069720 PMCID: PMC8160922 DOI: 10.3390/molecules26103040] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/14/2021] [Accepted: 05/16/2021] [Indexed: 11/30/2022] Open
Abstract
The phytochemical analysis of Vinca minor, V. herbacea, V. major, and V. major var. variegata leaf extracts showed species-dependent antioxidant, antibacterial, and cytotoxic effects correlated with the identified phytoconstituents. Vincamine was present in V. minor, V. major, and V. major var. variegata, while V. minor had the richest alkaloid content, followed by V. herbacea. V. major var. variegata was richest in flavonoids and the highest total phenolic content was found in V. herbacea which also had elevated levels of rutin. Consequently, V. herbacea had the highest antioxidant activity followed by V. major var. variegata. Whereas, the lowest one was of V. major. The V. minor extract showed the most efficient inhibitory effect against both Staphylococcusaureus and E. coli. On the other hand, V. herbacea had a good anti-bacterial potential only against S. aureus, which was most affected at morphological levels, as indicated by scanning electron microscopy. The Vinca extracts acted in a dose-depended manner against HaCaT keratinocytes and A375 melanoma cells and moreover, with effects on the ultrastructure, nitric oxide concentration, and lactate dehydrogenase release. Therefore, the Vinca species could be exploited further for the development of alternative treatments in bacterial infections or as anticancer adjuvants.
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Christensen SB. Natural Products That Changed Society. Biomedicines 2021; 9:biomedicines9050472. [PMID: 33925870 PMCID: PMC8146924 DOI: 10.3390/biomedicines9050472] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/18/2021] [Accepted: 04/24/2021] [Indexed: 12/24/2022] Open
Abstract
Until the end of the 19th century all drugs were natural products or minerals. During the 19th century chemists succeeded in isolating pure natural products such as quinine, morphine, codeine and other compounds with beneficial effects. Pure compounds enabled accurate dosing to achieve serum levels within the pharmacological window and reproducible clinical effects. During the 20th and the 21st century synthetic compounds became the major source of drugs. In spite of the impressive results achieved within the art of synthetic chemistry, natural products or modified natural products still constitute almost half of drugs used for treatment of cancer and diseases like malaria, onchocerciasis and lymphatic filariasis caused by parasites. A turning point in the fight against the devastating burden of malaria was obtained in the 17th century by the discovery that bark from trees belonging to the genus Cinchona could be used for treatment with varying success. However isolation and use of the active principle, quinine, in 1820, afforded a breakthrough in the treatment. In the 20th century the synthetic drug chloroquine severely reduced the burden of malaria. However, resistance made this drug obsolete. Subsequently artemisinin isolated from traditional Chinese medicine turned out to be an efficient antimalarial drug overcoming the problem of chloroquine resistance for a while. The use of synthetic analogues such as chloroquine or semisynthetic drugs such as artemether or artesunate further improved the possibilities for healing malaria. Onchocerciasis (river blindness) made life in large parts of Africa and South America miserable. The discovery of the healing effects of the macrocyclic lactone ivermectin enabled control and partly elimination of the disease by annual mass distribution of the drug. Also in the case of ivermectin improved semisynthetic derivatives have found their way into the clinic. Ivermectin also is an efficient drug for treatment of lymphatic filariasis. The serendipitous discovery of the ability of the spindle toxins to control the growth of fast proliferating cancer cells armed physicians with a new efficient tool for treatment of some cancer diseases. These possibilities have been elaborated through preparation of semisynthetic analogues. Today vincristine and vinblastine and semisynthetic analogues are powerful weapons against cancer diseases.
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Affiliation(s)
- Søren Brøgger Christensen
- The Museum of Natural Medicine & The Pharmacognostic Collection, University of Copenhagen, DK-2100 Copenhagen, Denmark
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Wahab NZA, Azizul A, Ibrahim N. Phytochemistry, cytotoxicity and antiviral activity of Catharanthus roseus. IRANIAN JOURNAL OF MICROBIOLOGY 2021; 12:460-465. [PMID: 33604002 PMCID: PMC7867705 DOI: 10.18502/ijm.v12i5.4608] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
Background and Objectives: Catharanthus roseus is generally used to treat many diseases in folklore remedies. The present study is aimed at determining phytochemical constituents, cytotoxicity and antiviral activities for crude extract of the plant. Materials and Methods: The whole plant of C. roseus was extracted using methanol extraction method. Phytochemical qualitative screening was carried out for C. roseus extract according to standard procedures used to test for the presence of alkaloid, saponin, terpenoid and steroid. Cytotoxicity was assessed using 3-(4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT) assay. Plaque reduction assays were carried out to evaluate the antiviral activity of C. roseus extract against herpes simplex virus type 1 (HSV-1). These include post-treatment, pre-treatment and virucidal assays. Results: C. roseus extract contain secondary metabolites such as alkaloid, saponin and terpenoid but does not contain steroid. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract of C. roseus was 0.5 mg/mL. The extract prepared from C. roseus possesses phytochemical compound that was non-cytotoxic to the cell with potential antiviral activity. Plaque reduction assays against herpes simplex virus type 1 (HSV-1) showed that the selective indices (SI = CC50 / EC50) of C. roseus extract in post-treatment, pre-treatment and virucidal assays were 36, 20 and 4.7 respectively. The results revealed that the extract prepared from C. roseus possesses phytochemical compound that was non-cytotoxic to the cell with potential antiviral activity. Conclusion: This study showed that C. roseus extract has promising potential to be explored as anti-HSV-1 agent regardless of the mode of treatment.
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Affiliation(s)
- Noor Zarina Abd Wahab
- Department of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Terengganu, Malaysia
| | - Aziah Azizul
- Department of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Terengganu, Malaysia
| | - Nazlina Ibrahim
- Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan, Bangi, Malaysia
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Garcia-Oliveira P, Otero P, Pereira AG, Chamorro F, Carpena M, Echave J, Fraga-Corral M, Simal-Gandara J, Prieto MA. Status and Challenges of Plant-Anticancer Compounds in Cancer Treatment. Pharmaceuticals (Basel) 2021; 14:ph14020157. [PMID: 33673021 PMCID: PMC7918405 DOI: 10.3390/ph14020157] [Citation(s) in RCA: 111] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/03/2021] [Accepted: 02/06/2021] [Indexed: 12/12/2022] Open
Abstract
Nowadays, cancer is one of the deadliest diseases in the world, which has been estimated to cause 9.9 million deaths in 2020. Conventional treatments for cancer commonly involve mono-chemotherapy or a combination of radiotherapy and mono-chemotherapy. However, the negative side effects of these approaches have been extensively reported and have prompted the search of new therapeutic drugs. In this context, scientific community started to look for innovative sources of anticancer compounds in natural sources, including traditional plants. Currently, numerous studies have evaluated the anticancer properties of natural compounds derived from plants, both in vitro and in vivo. In pre-clinical stages, some promising compounds could be mentioned, such as the sulforaphane or different phenolic compounds. On the other hand, some phytochemicals obtained positive results in clinical stages and were further approved for cancer treatment, such as vinca alkaloids or the paclitaxel. Nevertheless, these compounds are not exempt of limitations, such as low solubility, restricted effect on their own, negative side-effects, etc. This review aims to compile the information about the current phytochemicals used for cancer treatment and also promising candidates, main action mechanisms and also reported limitations. In this sense, some strategies to face the limitations have been considered, such as nano-based formulations to improve solubility or chemical modification to reduce toxicity. In conclusion, although more research is still necessary to develop more efficient and safe phytochemical drugs, more of these compounds might be used in future cancer therapies.
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Affiliation(s)
- Paula Garcia-Oliveira
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
- Centro de Investigação de Montanha (CIMO), Campus de Santa Apolonia, Instituto Politécnico de Bragança, 5300-253 Bragança, Portugal
| | - Paz Otero
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
| | - Antia Gonzalez Pereira
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
- Centro de Investigação de Montanha (CIMO), Campus de Santa Apolonia, Instituto Politécnico de Bragança, 5300-253 Bragança, Portugal
| | - Franklin Chamorro
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
| | - Maria Carpena
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
| | - Javier Echave
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
| | - Maria Fraga-Corral
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
- Centro de Investigação de Montanha (CIMO), Campus de Santa Apolonia, Instituto Politécnico de Bragança, 5300-253 Bragança, Portugal
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
- Correspondence: (J.S.-G.); (M.A.P.)
| | - Miguel Angel Prieto
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E-32004 Ourense, Spain; (P.G.-O.); (P.O.); (A.G.P.); (F.C.); (M.C.); (J.E.); (M.F.-C.)
- Correspondence: (J.S.-G.); (M.A.P.)
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Transcriptional analyses of the effects of Catharanthus roseus L. medicinal plant extracts on some markers related to obesity and inflammation in 3T3-L1 mouse cell lines. Biologia (Bratisl) 2021. [DOI: 10.2478/s11756-020-00567-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Abstract
Catharanthus roseus (C. roseus) is an important medicinal plant distributed in many countries. It has attracted increasing attention due to it being shown to possess a range of phytochemicals with various biological activities such as antioxidant, antibacterial, antifungal, antidiabetic and anticancer properties. Remarkably, vinblastine and vincristine isolated from this plant were the first plant-derived anticancer agents deployed for clinical use. Recently, new isolated indole alkaloids from this plant including catharoseumine, 14′,15′-didehydrocyclovinblastine, 17-deacetoxycyclovinblastine and 17-deacetoxyvinamidine effectively inhibited human cancer cell lines in vitro. Moreover, vindoline, vindolidine, vindolicine and vindolinine isolated from C. roseus leaf exhibited in vitro antidiabetic property. These findings strongly indicate that this plant is still a promising source of bioactive compounds, which should be further investigated. This paper provides an overview of the traditional use and phytochemical profiles of C. roseus, and summarises updated techniques of the preparation of dried material, extraction and isolation of bioactive compounds from this plant. In addition, purported health benefits of the extracts and bioactive compounds derived from this plant were also addressed to support their potential as therapeutic agents.
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Koel M, Kuhtinskaja M, Vaher M. Extraction of bioactive compounds from Catharanthus roseus and Vinca minor. Sep Purif Technol 2020. [DOI: 10.1016/j.seppur.2020.117438] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Khataee E, Karimi F, Razavi K. Different carbon sources and their concentrations change alkaloid production and gene expression in Catharanthus roseus shoots in vitro. FUNCTIONAL PLANT BIOLOGY : FPB 2020; 48:40-53. [PMID: 32690131 DOI: 10.1071/fp19254] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 06/29/2020] [Indexed: 05/24/2023]
Abstract
To compare the effects of different carbon sources on physiological aspects, especially medicinal alkaloid biosynthesis and related gene expression in Catharantus roseus (L.) G.Don, we employed sucrose and sorbitol with two concentrations (87.64 mM, the equimolar concentration of sucrose in MS basal medium, and 150 mM) on the plant's shoots in vitro in presence of 100 μM methyl jasmonate. The production of plant alkaloids including vincristine, vinblastine, ajmalicine, vindoline and catharantine and their biosynthetic and regulatory gene expression was measured. Both treatments had incremental effects on alkaloid production, upregulated the mitogen-activated protein kinase3 (MAPK3) and a downstream responsive transcription factor, ORCA3, which resulted in elevated transcript contents of the important genes in terpenoid indol alkaloids biosynthetic pathway including peroxidase1 (PRX1), geissoschizine synthase (GS), strictosidine synthase (STR) and deacetylvindoline acetyltransferase (DAT). Defensive responses such as antioxidant enzymes (catalase, peroxidase and superoxide dismutase) activities and non-enzymatic metabolites (total phenolics, flavonoids and carotenoids) contents increased under both treatments but the effects of sorbitol were stronger. Reduced fresh weight and chlorophylls contents, increased malondialdehyde (MDA) and carotenoid contents were shown after a week under all employed treatments. It seems that replacement of sucrose with sorbitol and also, increased concentrations of both carbon sources via increasing osmotic pressure make stressful conditions for the plant especially in longer times.
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Affiliation(s)
- Elham Khataee
- Department of Biology, Faculty of Basic Sciences, Shahed University, 3319118651, Tehran, Iran
| | - Farah Karimi
- Department of Biology, Faculty of Basic Sciences, Shahed University, 3319118651, Tehran, Iran; and Corresponding author.
| | - Khadijeh Razavi
- National institute of Genetic Engineering and Biotechnology, 1497716316, Tehran, Iran
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Gupta PSS, Bhat HR, Biswal S, Rana MK. Computer-aided discovery of bis-indole derivatives as multi-target drugs against cancer and bacterial infections: DFT, docking, virtual screening, and molecular dynamics studies. J Mol Liq 2020. [DOI: 10.1016/j.molliq.2020.114375] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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