Synthesis and Evaluation of a Series of 1,3,4-Thiadiazole Derivatives as Potential Anticancer Agents.

BACKGROUND AND METHODS In an attempt to develop potent antitumor agents, the synthesis of a series of N-(6-substituted benzothiazol-2-yl)-2-[(5-(arylamino)-1,3,4-thiadiazol-2-yl)thio]acetamides (1-14) was described and their cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma, HepG2 human hepatocellular carcinoma and NIH/3T3 mouse embryonic fibroblast cell lines were investigated using MTT assay. RESULTS Phenyl-substituted compounds (8-14) were found to be more effective than naphthyl-substituted compounds (1-7) on cancer cells. Compounds 8, 9, 10, 12, 13 and 14 were identified as the most potent anticancer agents on MCF-7 and HepG2 cell lines and therefore their effects on DNA synthesis and apoptosis/necrosis in MCF-7 cell line were evaluated. Among these compounds, N-(6-methoxybenzothiazol-2-yl)-2-[(5- (phenylamino)-1,3,4-thiadiazol-2-yl)thio]acetamide (13) was the most selective anticancer agent against MCF-7 and HepG2 cell lines with a SI value of 100. On the other hand, compounds 8, 9, 10, 12, 13 and 14 inhibited DNA synthesis in MCF-7 cell line in a dose-dependent manner. Flow cytometric analyses clearly indicated that the compounds showed significant anticancer activity against MCF-7 cell line via the induction of apoptosis dose dependently. CONCLUSION According to in vitro assays, compounds 8, 9, 10, 12, 13 and 14 stand out as promising candidates for further studies.

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