title: Microbial transformation of contraceptive drug etonogestrel into new metabolites with Cunninghamella blakesleeana and Cunninghamella echinulata.
abstract: Biotransformation of a steroidal contraceptive drug, etonogestrel (1), (13-ethyl-17β-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one) was investigated with Cunninghamella blakesleeana and C. echinulata. Five metabolites 2-6 were obtained on incubation of 1 with Cunninghamella blakesleeana, and three metabolites, 2, 4, and 6 were isolated from the transformation of 1 with C. echinulata. Among them, metabolites 2-4 were identified as new compounds. Their structures were deduced as 6β-hydroxy-11,22-epoxy-etonogestrel (2), 11,22-epoxy-etonogestrel (3), 10β-hydroxy-etonogestrel (4), 6β-hydroxy-etonogestrel (5), and 14α-hydroxy-etonogestrel (6). Compounds 1-6 were evaluated for various biological activities. Interestingly, compound 5 was found to be active against β-glucuronidase enzyme with IC50value of 13.97±0.12μM, in comparison to standard compound, d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Intestinal bacteria produce β-glucuronidase. Increased activity of β-glucuronidase is responsible for the hydrolyses of glucuronic acid conjugates of estrogen and other toxic substances in the colon, which plays a key role in the etiology of colon cancer. Inhibition of β-glucoronidase enzyme therefore has a therapeutic significance. Compounds 1-6 were also found to be non cytotoxic against 3T3 mouse fibroblast cell lines.
authors: Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon. Electronic address: eliasbay@aub.edu.lb.
authors: Elias
authors: E
authors: Baydoun
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors: Atia-Tul
authors: AT
authors: Wahab
authors: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors: Nayab
authors: N
authors: Shoaib
authors: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors: Malik Shoaib
authors: MS
authors: Ahmad
authors: Department of Biology, University of Balamand, Tripoli, Lebanon.
authors: Roula
authors: R
authors: Abdel-Massih
authors: Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
authors: Colin
authors: C
authors: Smith
authors: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors: Nimra
authors: N
authors: Naveed
authors: 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 University, Jeddah 21412, Saudi Arabia. Electronic address: iqbal.choudhary@iccs.edu.
authors: M Iqbal
authors: MI
authors: Choudhary
mesh_terms: D016475:3T3 Cells; D000818:Animals; D003270:Contraceptive Agents / Q000737:chemistry / Q000378:metabolism*; D020093:Cunninghamella / Q000378:metabolism*; D017135:Desogestrel / Q000737:chemistry / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure
chemical_list: D003270:Contraceptive Agents; C044815:etonogestrel; D017135:Desogestrel; D005966:Glucuronidase
keywords: Biotransformation; Colon cancer; Contraceptive; Cunninghamella blakesleeana; Cunninghamella echinulata; Etonogestrel; β-Glucuronidase inhibition