Cytotoxic, Apoptotic and DNA Synthesis Inhibitory Effects of Some Thiazole Derivatives

Title:Cytotoxic, Apoptotic and DNA Synthesis Inhibitory Effects of Some Thiazole Derivatives

Volume: 14 Issue: 5

Author(s): Gulsen Akalın Ciftci, Mehlika Dilek Altıntop*, Halide Edip Temel, Ahmet Ozdemir and Zafer Asım Kaplancıklı

Affiliation:

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

Keywords: Thiazole, imidazole, triazole, cancer, DNA synthesis, apoptosis, mitochondrial membrane potential, acetylcholinesterase, butyrylcholinesterase.

Abstract: Background: Cancer is one of the leading causes of morbidity and mortality worldwide and extensive efforts have been devoted to the discovery of new anticancer agents. In the last few decades, the clinical efficacy of tiazofurin and its analogues, dasatinib and bleomycins has pointed out the importance of thiazole moiety in the field of cancer treatment.

Methods: In the present paper, some thiazolyl hydrazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cell lines using MTT assay. The most effective compounds were also investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. In order to investigate the relationship between anticancer activity and cholinesterases, all compounds were evaluated for their ability to inhibit AChE and BuChE using a modification of Ellman’s spectrophotometric method.

Results: Generally, the compounds showed more potent inhibitory effects on C6 cells than A549 cells. 2- [2-(4-(1H-1,2,4-Triazol-1-yl)benzylidene)hydrazinyl]-4-(4-nitrophenyl)thiazole (2) was the most promising agent due to its notable inhibitory effect on C6 cells with an IC50 value of 13.00±1.00 μg/mL when compared with cisplatin (IC50= 12.67±3.06 μg/mL) and low cytotoxicity against NIH/3T3 cell line (IC50= 733.33±256.58 μg/mL). DNA synthesis inhibition percent of compound 2 was 62.2%, whereas the inhibition percent of cisplatin was 53.95%. Compound 2 increased early and late apoptotic cell population (18.3%) more than cisplatin (16.3%). This compound also caused disturbance on mitochondrial membrane potential (40.2%) in C6 cells, which was similar to cisplatin (42.3%).

Conclusion: Compound 2, the most promising antitumor agent against C6 cells in this series, did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between the anticancer activity of compound 2 and cholinesterases.

Cite this article as:

Ciftci Akalın Gulsen, Altıntop Dilek Mehlika*, Temel Edip Halide, Ozdemir Ahmet and Kaplancıklı Asım Zafer, Cytotoxic, Apoptotic and DNA Synthesis Inhibitory Effects of Some Thiazole Derivatives, Letters in Drug Design & Discovery 2017; 14 (5) . https://dx.doi.org/10.2174/1570180813666160907170553

DOI https://dx.doi.org/10.2174/1570180813666160907170553	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X