Microbial-catalysed derivatization of anti-cancer drug exemestane and cytotoxicity of resulting metabolites against human breast adenocarcinoma cell line (MCF-7) in vitro

摘要

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-5 alpha-androstane-3 beta,16 beta,17 beta-triol (2), 17 beta-hydroxy-6-methyleneandrosta-4-ene-3-one (3), 6 alpha-spiroxirandrost-4-ene-3,17-dione (4), 6-methyleneandrosta-4-ene-3,17-dione (5), 6 beta,17 beta-dihydroxyandrost-4-en-3-one (6), 17 beta-hydroxy-6 alpha-spiroxirandrost-1,4-diene-3-one (7), 17 beta-hydroxy-6 alpha-hydroxymethylandrosta-1,4-dien-3-one (8), 6 alpha-hydroxymethylandrosta-1,4-diene-3,17-dione (9), 17 beta-hydroxy-6-methyleneandrosta-1,4-diene-3,16-dione (10), 6 alpha-hydroxy-4-androstene-3,17-dione (11), and 6 alpha-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 IC50 of 33.43 +/- 4.01 mu M, in comparison to the standard anti-cancer drug, doxorubicin (IC50 = 0.92 +/- 0.1 mu M). (C) 2016 Elsevier Inc. All rights reserved.