Microbial transformation of danazol with Cunninghamella blakesleeana and anti-cancer activity of danazol and its transformed products

Abstract

Biotransformation of danazol (1) (17beta-hydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole) with Cunninghamella blakesleeana yielded three new metabolites 2-4 and a known metabolite 5. These metabolites were identified as 14beta,17beta-dihydroxy-2-(hydroxymethyl)-17alpha-pregn-4-en-20-yn-3-one (2), 1alpha,17beta-dihydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (3), 6beta,17beta-dihydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (4), and 17beta-hydroxy-2-(hydroxymethyl)-17alpha-pregn-1,4-dien-20-yn-3-one (5). Danazol (1) and its derivatives were evaluated against cervical cancer cell line (HeLa). Compound 1 showed a potent cytotoxicity with IC50=0.283+/-0.013 muM, as compared to doxorubicin (IC50=0.506+/-0.015 muM), where compound 3 was also found to be significantly active with IC50=13.427+/-0.819 muM.