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

• Biotransformation of danazol (1) was investigated with Cunninghamella blakesleeana.
• Metabolites 2–4 were found to be new.
• Compounds 1–5 were evaluated against HeLa cervical cancer cell line.
• Danazol (1) and metabolite 3 showed cytotoxicity against the HeLa cell line.

Biotransformation of danazol (1) (17β-hydroxy-17α-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 14β,17β-dihydroxy-2-(hydroxymethyl)-17α-pregn-4-en-20-yn-3-one (2), 1α,17β-dihydroxy-17α-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (3), 6β,17β-dihydroxy-17α-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (4), and 17β-hydroxy-2-(hydroxymethyl)-17α-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 μM, as compared to doxorubicin (IC50 = 0.506 ± 0.015 μM), where compound 3 was also found to be significantly active with IC50 = 13.427 ± 0.819 μM.

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