Design, synthesis of new thiazole derivatives and studies on their targeted anticancer activity

In this study, fourteen new thiazolyl hydrazone derivatives (2a-n) were synthesized and the structures of these compounds were confirmed using spectroscopic methods. The in vitro cytotoxic effects of all compounds on A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells were determined by means of MTT assay. The effects of the compounds with selective anticancer activity on apoptosis and Akt were also investigated. 2-[2-((Isoquinolin-5-yl)methylene)hydrazinyl]-4-(4-methylsulfonylphenyl)thiazole (2k) (IC50= 1.43±0.12 µM) and 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]-4-(1,3-benzodioxol-5-yl)thiazole (2l) (IC50= 1.75±0.07 µM) showed stronger anticancer potency than cisplatin (IC50= 3.90±0.10 µM) on A549 cells; 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]-4-(4-methoxyphenyl)thiazole (2j) (IC50= 3.93±0.06 µM) showed anticancer activity close to cisplatin. These compounds were found to induce apoptosis more in A549 cells compared to control. Compound 2j (IC50= 3.55±0.64 µM) showed stronger Akt inhibitory activity than GSK690693 (IC50= 4.93±0.06 µM), while compounds 2k and 2l did not cause Akt inhibition at IC50 concentrations (1.43 and 1.75 µM, respectively). As a result of in vitro studies, it was determined that compound 2j showed its cytotoxic and apoptotic effects on A549 cell line via Akt inhibition. However, it is understood that compounds 2k and 2l exert their strong anticancer effects on A549 cells through different pathways.