title: Microbial-catalysed derivatization of anti-cancer drug exemestane and cytotoxicity of resulting metabolites against human breast adenocarcinoma cell line (MCF-7) in vitro.
abstract: Structural transformation of anticancer drug exemestane (1) with fungi Cunninghamella blakesleeana (ATCC 8688A), Curvularia lunata (ATCC 12017), Aspergillus niger (ATCC 10549), and Gibberella fujikuroi (ATCC 10704) yielded eleven metabolites 2-12, in which 2 and 8 were identified as new. Their structures were characterized as 6-methylene-5α-androstane-3β,16β,17β-triol (2), 17β-hydroxy-6-methyleneandrosta-4-ene-3-one (3), 6α-spiroxirandrost-4-ene-3,17-dione (4), 6-methyleneandrosta-4-ene-3,17-dione (5), 6β,17β-dihydroxyandrost-4-en-3-one (6), 17β-hydroxy-6α-spiroxirandrost-1,4-diene-3-one (7), 17β-hydroxy-6α-hydroxymethylandrosta-1,4-dien-3-one (8), 6α-hydroxymethylandrosta-1,4-diene-3,17-dione (9), 17β-hydroxy-6-methyleneandrosta-1,4-diene-3,16-dione (10), 6α-hydroxy-4-androstene-3,17-dione (11), and 6α-hydroxymethylandrost-4-ene-3,17-dione (12). Substrate 1, and its transformed products were evaluated for their cytotoxicity against breast cancer cell line (MCF-7). Compound 3 was found to be moderately active with an IC50of 33.43±4.01μM, in comparison to the standard anti-cancer drug, doxorubicin (IC50=0.92±0.1μM).
authors: University of Iowa Hospital and Clinics, Iowa City, IA 52242, United States.
authors: Serine
authors: S
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: Saira
authors: S
authors: Bano
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors: Rehan
authors: R
authors: Imad
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: D000730:Androstadienes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001234:Aspergillus niger / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D020093:Cunninghamella / Q000378:metabolism; D005285:Fermentation; D005874:Gibberella / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; C056516:exemestane
keywords: Aspergillus niger; Breast cancer (MCF-7) cell line; Cunninghamella blakesleeana; Curvularia lunata; Exemestane; Gibberella fujikuroi