Microbial transformation of anti-cancer steroid and cytotoxicity of its metabolites against cancer cell lines -

Abstract

Microbial transformation of steroids has been extensively employed over the last decades for the production of novel drug analogues that are hardly synthesized by the classical chemical routes. Exemestane is a steroidal drug used to treat breast cancer by irreversibly binding to the aromatase enzyme responsible for the conversion of androgen to estrogen in postmenopausal women. Microbial transformation of exemestane (1) was investigated using the two fungal strains Macrophomina phaseolina and Fusarium lini. Biotransformation of the drug in Fusarium lini yielded only one metabolite 11α-hydroxy-6-methylene-androsta-1, 4-diene-3,17-dione (2); however it yielded three metabolites 16β, 17β-dihydroxy-6-methylene-androsta-1, 4-diene-3-one (3), 17β-hydroxy-6-methylene-androsta-1, 4-diene-3, 16-dione (4), and 17β-hydroxy-6-methylene-androsta-1, 4-diene-3-one (5) when performed in Macrophomina phaseolina. Metabolites (2), (3), and (4) are new compounds reported for the first time in this project, while metabolite (5) was previously described. Upon testing the metabolites against cancer cell lines of cervical and prostate origins, metabolite (2) was found to be moderately active.