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

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

Volume: 18 Issue: 11

Author(s): Mehlika D. Altıntop*, Belgin Sever, Ahmet Özdemir, Sinem Ilgın, Özlem Atlı, Gülhan Turan-Zitouni and Zafer A. Kaplancıklı

Affiliation:

• Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir,Turkey

Keywords: Benzothiazole, thiadiazole, anticancer activity, apoptosis, DNA synthesis, human hepatocellular carcinoma.

Abstract: 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.

Cite this article as:

Altıntop D. Mehlika *, Sever Belgin , Özdemir Ahmet , Ilgın Sinem , Atlı Özlem, Turan-Zitouni Gülhan and Kaplancıklı A. Zafer , Synthesis and Evaluation of a Series of 1,3,4-Thiadiazole Derivatives as Potential Anticancer Agents, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (11) . https://dx.doi.org/10.2174/1871520618666180509111351