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
Conclusion: According to in vitro assays, compounds 8, 9, 10, 12, 13 and 14 stand out as promising candidates
for further studies.