Microbial transformation of three bufadienolides by Nocardia sp. and some insight for the cytotoxic structure-activity relationship (SAR).
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.
Zhang
Jian
J
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, People's Republic of China.
Sun
Yang
Y
Liu
Ji-Hua
JH
Yu
Bo-Yang
BY
Xu
Qiang
Q
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
C527739:3-acetyl 15beta-hydroxyl bufotalin; D000970:Antineoplastic Agents; D002018:Bufanolides; C087925:bufadienolide; C005734:bufogenin; C002471:cinobufagin; C022777:bufalin