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

摘要

Biotransformation of danazol (1) (17 beta-hydroxy-17 alpha-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 14 beta,17 beta-dihydroxy-2-(hydroxymethyl)-17 alpha-pregn-4-en-20-yn-3-one (2), 1 alpha,17 beta-dihydroxy-17 alpha-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (3), 6 beta,17 beta-dihydroxy-17 alpha-apregna-2,4-dien-20-yno-[2,3-d]-isoxazole (4), and 17 beta-hydroxy-2-(hydroxymethyl)-17 alpha-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 mu M, as compared to doxorubicin (IC50=0.506 +/- 0.015 mu M), where compound 3 was also found to be significantly active with IC50 = 13.427 +/- 0.819 mu M. (C) 2015 Elsevier Inc. All rights reserved.