Chatterjee P, Kouzi S A, Pezzuto J M, Hamann M T
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209, USA.
Appl Environ Microbiol. 2000 Sep;66(9):3850-5. doi: 10.1128/AEM.66.9.3850-3855.2000.
Microbial transformation of the antimelanoma agent betulinic acid was studied. The main objective of this study was to utilize microorganisms as in vitro models to predict and prepare potential mammalian metabolites of this compound. Preparative-scale biotransformation with resting-cell suspensions of Bacillus megaterium ATCC 13368 resulted in the production of four metabolites, which were identified as 3-oxo-lup-20(29)-en-28-oic acid, 3-oxo-11alpha-hydroxy-lup-20(29)-en-28-oic acid, 1beta-hydroxy-3-oxo-lup-20(29)-en-28-oic acid, and 3beta,7beta, 15alpha-trihydroxy-lup-20(29)-en-28-oic acid based on nuclear magnetic resonance and high-resolution mass spectral analyses. In addition, the antimelanoma activities of these metabolites were evaluated with two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid).
研究了抗黑素瘤药物桦木酸的微生物转化。本研究的主要目的是利用微生物作为体外模型来预测和制备该化合物潜在的哺乳动物代谢产物。用巨大芽孢杆菌ATCC 13368的静息细胞悬浮液进行制备规模的生物转化,产生了四种代谢产物,基于核磁共振和高分辨率质谱分析,它们被鉴定为3-氧代羽扇-20(29)-烯-28-酸、3-氧代-11α-羟基羽扇-20(29)-烯-28-酸、1β-羟基-3-氧代羽扇-20(29)-烯-28-酸和3β,7β,15α-三羟基羽扇-20(29)-烯-28-酸。此外,用两种人黑素瘤细胞系Mel-1(淋巴结)和Mel-2(胸水)评估了这些代谢产物的抗黑素瘤活性。