Isolation,identification, and bioactivity of microbial metabolites of cyclopamine and its congeners |
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| Affiliation: | 1. Department of Natural Product Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China;2. School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, PR China;3. Shanghai Institute of Pharmaceutical Industry, Shanghai 200400, PR China;1. Recherche et innovation en chimie médicinale (RICM, ISP-UMR 1282), faculté de pharmacie, université François-Rabelais, 31, avenue Monge, 37200 Tours, France;2. Biocodex, centre de recherche, ZAC de Mercière, chemin d’Armancourt, 60200 Compiègne, France;3. Laboratoire de chimie physique, faculté de pharmacie, université Paris-Descartes, 4, avenue de l’observatoire, case 23, 75006 Paris, France;1. Biology Faculty, M.V. Lomonosov Moscow State University, Moscow, Russia;2. MSU Institute of Mitoengineering LLC, Moscow, Russia;3. Institute for Biomedical problems RAS, Moscow, Russia;4. Pelvipharm/INSERM U1179, Montigny-Le-Bretonneux, France;5. Aivix Ltd, Moscow, Russia;1. Entomology Research Institute, Loyola College, Chennai, 600 034, Tamil Nadu, India;2. Department of Ecotoxicology, International Institute for Biotechnology and Toxicology (IIBAT), Padappai, Kancheepuram, 601 301, Tamil Nadu, India;3. Addiriyah Chair for Environmental Studies, Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box. 2455, Riyadh, 11451, Saudi Arabia;4. Department of Zoology, University of Madras, Chennai, 600 025, Tamil Nadu, India;5. Department of Agriculture, Food and Environment, University of Pisa, Via del Borghetto 80, Pisa, 56124, Italy;1. Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, Yunnan, PR China;2. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, University of Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China |
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| Abstract: | The biotransformation of cyclopamine (1) and its congeners (2, 3 and 4) by Cunninghamella echinulata (ACCC 30369) was investigated. The chemical structures of two new congeners (2 and 4) and nine new metabolites were elucidated by 1D NMR (1H, 13C and DEPT), 2D NMR (COSY, HMBC, HSQC and NOESY) and HRESIMS analyses and further confirmed by X-ray diffraction studies. Among these compounds, 2 and 4 showed moderate cytotoxicity in HepG2 cells (2, IC50 = 8.03 ± 1.92 μM) and A549 cells (4, IC50 = 10.19 ± 2.18 μM). Conversely, the cytotoxicity of the nine metabolites was sharply reduced. Similar to 1, compound 4 induced a cyclopia phenotype in zebrafish embryos at 20 μM. Moreover, compound 4 was more stable than 1 in an acidic environment. |
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| Keywords: | Biotransformation Cyclopamine Cyclopamine congeners |
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