title: Aspergillus niger-mediated biotransformation of methenolone enanthate, and immunomodulatory activity of its transformed products.
abstract: Two fungal cultures Aspergillus niger and Cunninghamella blakesleeana were used for the biotransformation of methenolone enanthate (1). Biotransformation with A. niger led to the synthesis of three new (2-4), and three known (5-7) metabolites, while fermentation with C. blakesleeana yielded metabolite 6. Substrate 1 and the resulting metabolites were evaluated for their immunomodulatory activities. Substrate 1 was found to be inactive, while metabolites 2 and 3 showed a potent inhibition of ROS generation by whole blood (IC50=8.60 and 7.05μg/mL), as well as from isolated polymorphonuclear leukocytes (PMNs) (IC50=14.0 and 4.70μg/mL), respectively. Moreover, compound 3 (34.21%) moderately inhibited the production of TNF-α, whereas 2 (88.63%) showed a potent inhibition of TNF-α produced by the THP-1 cells. These activities indicated immunomodulatory potential of compounds 2 and 3. All products were found to be non-toxic to 3T3 mouse fibroblast cells.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Hussain
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: Nida
authors.initials: N
authors.lastname: Dastagir
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Shabbir
authors.initials: S
authors.lastname: Hussain
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: Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan.
authors.forename: Salman
authors.initials: S
authors.lastname: Zafar
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: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Saira
authors.initials: S
authors.lastname: Bano
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Wajid
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 Universisty, Jeddah 21412, Saudi Arabia. Electronic address: iqbal.choudhary@iccs.edu.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D000328:Adult; D001234:Aspergillus niger / Q000378:metabolism*; D001711:Biotransformation; D002478:Cells, Cultured; D020093:Cunninghamella / Q000378:metabolism; D005285:Fermentation / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008710:Methenolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C028758:methenolone enanthate; D008710:Methenolone
keywords: Anabolic-androgenic steroids; Anti-inflammatory; Aspergillus niger; Biotransformation; Cunninghamella blakesleeana; Immunomodulatory; Methenolone enanthate; TNF-α inhibitors