title: Microbial transformation of three bufadienolides by Nocardia sp. and some insight for the cytotoxic structure-activity relationship (SAR).
abstract: Resibufogenin, cinobufagin, and bufalin are cytotoxic steroids isolated from the Chinese drug Chan'su. Biotransformation of these three bufadienolides by Nocardia sp. NRRL 5646 was investigated. Notably, resibufogenin was converted to 3-acetyl 15beta-hydroxyl bufotalin, via an unprecedented 14beta,15beta-epoxy ring cleavage and a regio-selective acetoxylation. This product showed significantly increased cytotoxic activity. The regio-selective acetylation of the 3-OH was also involved in the other reactions. The structures of metabolites were established by ESI-LC/MS and 2D NMR techniques. The in vitro cytotoxic activities against human cancer cell lines of the substrates and the transformed products were determined by the MTT method and their structure-activity relationship (SAR) was discussed. This investigation provided a useful approach to prepare new bufadienolides and the SAR research.
authors.affiliation: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Liu
authors.forename: Bo-Yang
authors.initials: BY
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D002018:Bufanolides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009615:Nocardia / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C527739:3-acetyl 15beta-hydroxyl bufotalin; D000970:Antineoplastic Agents; D002018:Bufanolides; C087925:bufadienolide; C005734:bufogenin; C002471:cinobufagin; C022777:bufalin