title: Biotransformation of dianabol with the filamentous fungi and β-glucuronidase inhibitory activity of resulting metabolites.
abstract: Biotransformation of the anabolic steroid dianabol (1) by suspended-cell cultures of the filamentous fungi Cunninghamella elegans and Macrophomina phaseolina was studied. Incubation of 1 with C. elegans yielded five hydroxylated metabolites 2-6, while M. phaseolina transformed compound 1 into polar metabolites 7-11. These metabolites were identified as 6β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (2), 15α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (3), 11α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (4), 6β,12β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), 6β,15α,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (6), 17β-hydroxy-17α-methylandrost-1,4-dien-3,6-dione (7), 7β,17β,-dihydroxy-17α-methylandrost-1,4-dien-3-one (8), 15β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (9), 17β-hydroxy-17α-methylandrost-1,4-dien-3,11-dione (10), and 11β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (11). Metabolite 3 was also transformed chemically into diketone 12 and oximes 13, and 14. Compounds 6 and 12-14 were identified as new derivatives of dianabol (1). The structures of all transformed products were deduced on the basis of spectral analyses. Compounds 1-14 were evaluated for β-glucuronidase enzyme inhibitory activity. Compounds 7, 13, and 14 showed a strong inhibition of β-glucuronidase enzyme, with IC50 values between 49.0 and 84.9 μM.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Naik T
authors.initials: NT
authors.lastname: Khan
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Salman
authors.initials: S
authors.lastname: Zafar
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Shagufta
authors.initials: S
authors.lastname: Noreen
authors.affiliation: Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Al Majid
authors.affiliation: Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Zeid A
authors.initials: ZA
authors.lastname: Al Othman
authors.affiliation: Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Saud Ibrahim
authors.initials: SI
authors.lastname: Al-Resayes
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: hej@cyber.net.pk.
authors.lastname: Atta-ur-Rahman
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D000818:Animals; D001711:Biotransformation; D017173:Caenorhabditis elegans / Q000187:drug effects; D005658:Fungi / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006900:Hydroxylation; D008696:Methandrostenolone / Q000737:chemistry*
chemical_list: D008696:Methandrostenolone; D005966:Glucuronidase
keywords: Anabolic steroid; Biotransformation; Cunninghamella elegans; Dianabol; Macrophomina phaseolina; β-Glucuronidase inhibition