Microbial biotransformation of anticancer drug Abiraterone acetate using Cunninghamella elegans
RESEARCH JOURNAL OF BIOTECHNOLOGY(2018)
摘要
Cunninghamella microbe is an effective in vitro model for the production of drug metabolites which is important for metabolic studies and in drug development. In this study, microbial screening and biotransformation of prostate anticancer drug Abiraterone acetate was performed using Cunninghamella species and the extracted crude compounds were analyzed by MASS Spectra and HPLC. Major metabolite was purified by preparative TLC and characterized by MASS,(1) HNMR and(13) CNMR spectra. Out of the seven strains, only Cunninghamella elegans NCIM 690 was able to transform the Abiraterone acetate. Using HPLC analysis, almost 98% of Abiraterone acetate metabolic conversion was observed. Known human metabolites with molecular weights of 347.9 and 526.2 were identified from MASS analysis. The purified metabolite M1 was confirmed as Delta(4)-Abiraterone by MASS (m/z 347.5), (HNMR)-H-1 and 13 CNMR. This study confirms that Cunninghamella elegans NCIM 690 is the best in vitro model for microbial biotransformation of Abiraterone acetate to its metabolite Delta(4)-Abiraterone, a known human metabolite, which can be used as a reference standard for the pharmacological/toxicological/clinical studies.
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关键词
Delta(4)-Abiraterone,Abiraterone acetate,Biotransformation,Cunninghamella elegans,Drug metabolite
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