Cunninghamella blakesleeana-mediated biotransformation of a contraceptive drug,desogestrel, and anti-MDR-Staphylococcus aureus activity of its metabolites |
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| Institution: | 1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. Aix Marseille Universite, CNRS, Centrale Marseille, iSm2, Marseille, France;4. Doctoral School of Science and Technology, Research Platform for Environmental Science (PRASE), Lebanese University, Lebanon;5. Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon;6. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia;1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan;2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan;3. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia;1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;3. Department of Chemistry, NED University of Engineering & Technology, Karachi 75270, Pakistan;4. Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University, Mardan, Mardan 23200, Pakistan;5. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia;1. Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon;2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;4. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia;1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia |
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| Abstract: | Staphylococcus aureus is one of the most infectious agents among staphylococcal bacteria. Currently many strains of S. aureus have developed resistance against available antibiotics. Therefore, the treatment of infections caused by them is a major challenge. During current study, desogestrel (1), a contraceptive drug, was found to be a potent growth inhibitor of drug resistant strains of S. aureus. Therefore, in search of new and effective agents against multi-drug resistant S. aureus strains, whole-cell bio-catalytic conversion of desogestrel (1) by Cunninghamella blakesleeana ATCC 8688A at pH 7.0 and 25 °C was carried out, yielding three new metabolites, 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6β,15β,17β-triol (2), 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3β,6β,17β-triol (3), and 13-ethyl-11-methylene-18,19-dinor-17α-pregn-20-yn-3α,5α,6β,17β-tetraol (4), along with a known metabolite, 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6β,17β-dihydroxy-3-one (5). Among them, compounds 1–2 showed a potent activity against S. aureus EMRSA-17, S. aureus NCTC 13277 (MRSA-252), and S. aureus NCTC 13143, and clinically isolated Pakistani strain of S. aureus in an in vitro Microplate Alamar Blue Assay (MABA). Vancomycin was used as the standard drug in this assay. In addition, compound 1 also showed a significant activity against vancomycin-resistant S. aureus (VRSA) ATCC 700699. Compounds 1–5 were also evaluated against 3T3 normal cell line (mouse fibroblast) where they all were identified as non-cytotoxic. The present study thus provides new leads for the development of anti-bacterial drugs against MDR S. aureus. |
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| Keywords: | Desogestrel Biotransformation Anti-bacterial Cytotoxicity |
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