title: Biotransformation of anabolic compound methasterone with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini, and TNF-α inhibitory effect of transformed products.
abstract: Microbial transformation of methasterone (1) was investigated with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini. Biotransformation of 1 with M. phaseolina yielded metabolite 2, while metabolites 3-7 were obtained from the incubation of 1 with C. blakesleeana. Metabolites 8-13 were obtained through biotransformation with F. lini. All metabolites, except 13, were found to be new. Methasterone (1) and its metabolites 2-6, 9, 10, and 13 were then evaluated for their immunomodulatory effects against TNF-α, NO, and ROS production. Among all tested compounds, metabolite 6 showed a potent inhibition of proinflammatory cytokine TNF-α (IC50=8.1±0.9μg/mL), as compared to pentoxifylline used as a standard (IC50=94.8±2.1μg/mL). All metabolites were also evaluated for the inhibition of NO production at concentration of 25μg/mL. Metabolites 6 (86.7±2.3%) and 13 (62.5±1.5%) were found to be the most potent inhibitors of NO as compared to the standard NG-monomethyl-l-arginine acetate (65.6±1.1%). All metabolites were found to be non-toxic against PC3, HeLa, and 3T3 cell lines. Observed inhibitory potential of metabolites 6 and 13 against pro-inflammatory cytokine TNF-α, as well as NO production makes them interesting leads for further studies.
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: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Sammer
authors.initials: S
authors.lastname: Yousuf
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.lastname: Atia-Tul-Wahab
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: Almas
authors.initials: A
authors.lastname: Jabeen
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
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; Dr. Panjwani Center for Molecular Medicine and Drug Research, 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: D016475:3T3 Cells; D000818:Animals; D001203:Ascomycota / Q000235:genetics; D001711:Biotransformation; D049109:Cell Proliferation / Q000187:drug effects; D020093:Cunninghamella / Q000235:genetics; D005670:Fusarium / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D045165:Testosterone Congeners / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D045165:Testosterone Congeners; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide
keywords: Anabolic-androgenic; Biotransformation; Cunninghamella blakesleeana; Fusarium lini; Macrophomina phaseolina; Methasterone