Journal
LETTERS IN DRUG DESIGN & DISCOVERY
Volume 11, Issue 3, Pages 256-264Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/15701808113106660080
Keywords
Cancer; Chromane; Hepatotoxicity; Imidazole; Thiazolidine-2,4-dione; Triazole; Troglitazone
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In the course of our ongoing program dedicated to the synthesis of anti-proliferative compounds, we prepared new troglitazone derivatives bearing a biphenyle moiety. The chromane heterocycle was further replaced by imidazole and triazole derivatives. Many compounds exhibited fair to high activity towards various cancer cell lines. Among them, compound 17b reduced cell viability leading to only 22-34% viable cells in four cancer cell lines at 10 mu M, but unfortunately also led to a low (13%) cell viability of non-malignant primary cultured human hepatocytes at 200 mu M. Interestingly, compound 11b also reduced cell viability in colon and liver cancer cell lines (29% and 24% cell viability respectively at 10 mu M), but maintained a high cell viability of non-malignant hepatocytes (reaching 71% cell viability at 200 mu M), thus exhibiting a huge selectivity.
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