title: Microbial transformation of danazol with Cunninghamella blakesleeana and anti-cancer activity of danazol and its transformed products.
abstract: 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.
authors.affiliation: Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon. Electronic address: eliasbay@aub.edu.lb.
authors.forename: Elias
authors.initials: E
authors.lastname: Baydoun
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: atiatulwahab@gmail.com.
authors.lastname: Atia-tul-Wahab
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Hina
authors.initials: H
authors.lastname: Mehmood
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Malik Shoaib
authors.initials: MS
authors.lastname: Ahmad
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Rizwana
authors.initials: R
authors.lastname: Malik
authors.affiliation: Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
authors.forename: Colin
authors.initials: C
authors.lastname: Smith
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia. Electronic address: iqbal.choudhary@iccs.edu.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D016923:Cell Death / Q000187:drug effects; D020093:Cunninghamella / Q000378:metabolism*; D003613:Danazol / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D003613:Danazol
keywords: Anti-cancer; Biotransformation; Cervical cancer cell line (HeLa); Cunninghamella blakesleeana; Cytotoxicity; Danazol