title: Microbial transformation of nandrolone with Cunninghamella echinulata and Cunninghamella blakesleeana and evaluation of leishmaniacidal activity of transformed products.
abstract: Therapeutic potential of nandrolone and its derivatives against leishmaniasis has been studied. A number of derivatives of nandrolone (1) were synthesized through biotransformation. Microbial transformation of nandrolone (1) with Cunninghamella echinulata and Cunninghamella blakesleeana yielded three new metabolites, 10β,12β,17β-trihydroxy-19-nor-4-androsten-3-one (2), 10β,16α,17β-trihydroxy-19-nor-4-androsten-3-one (3), and 6β,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with four known metabolites, 10β,17β-dihydroxy-19-nor-4-androsten-3-one (5), 6β,17β-dihydroxy-19-nor-4-androsten-3-one (6) 10β-hydroxy-19-nor-4-androsten-3,17-dione (7) and 16β,17β-dihydroxy-19-nor-4-androsten-3-one (8). Compounds 1-8 were evaluated for their anti-leishmanial activity. Compounds 1 and 8 showed a significant activity in vitro against Leishmania major. The leishmanicidal potential of compounds 1-8 (IC50=32.0±0.5, >100, 77.39±5.52, 70.90±1.16, 54.94±1.01, 80.23±3.39, 61.12±1.39 and 29.55±1.14 μM, respectively) can form the basis for the development of effective therapies against the protozoal tropical disease leishmaniasis.
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: Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
authors.forename: Martin
authors.initials: M
authors.lastname: Karam
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: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Mahwish Shafi Ahmed
authors.initials: MS
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: 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.lastname: Samreen
authors.affiliation: Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
authors.forename: Colin
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Biology, University of Balamand, Koura 100, Lebanon.
authors.forename: Roula
authors.initials: R
authors.lastname: Abdel-Massih
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 Universisty. Jeddah 21412, Saudi Arabia. Electronic address: iqbal.choudhary@iccs.edu.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001711:Biotransformation; D020093:Cunninghamella / Q000378:metabolism*; D018320:Leishmania major / Q000187:drug effects*; D009277:Nandrolone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D009277:Nandrolone
keywords: Anabolic compound; Cunninghamella blakesleeana; Cunninghamella echinulata; Leishmania major; Leishmanicidal activity; Nandrolone