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, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir
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.
