Synthesis of new thiazole derivatives with an indole ring and evaluation of their targeted anticancer effects on non-small cell lung cancer cells

In this study, twelve new thiazolyl hydrazone derivatives (1-12) were synthesized and the structures of these compounds were confirmed by spectroscopic methods. The cytotoxic effects of all compounds on A549 human lung adenocarcinoma cells were determined by MTT assay. All tested compounds were found to be more effective than erlotinib. In particular, compounds 2, 3 and 10 showed very strong anticancer effects on A549 cells. By evaluating the cytotoxic effects of these three compounds against K562 chronic myeloid leukemia and peripheral blood mononuclear cells, their selectivity index values were determined. Compounds 2, 3 and 10 were found to possess more selective anticancer activity than erlotinib. In vitro epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitory effects of these three derivatives were investigated. 2-[2-((5-Chloro-1H-indol-3-yl)methylene)hydrazinyl]-4-(4-nitrophenyl)thiazole (2) showed stronger EGFR TK inhibitory activity compared to other compounds. In addition, the inhibitory effects of this compound on different TK enzymes were also evaluated. Compound 2 showed better inhibitory activity especially on HER2, LCK, CSK, FYN A and IGF1R enzymes compared to erlotinib. This result indicates that compound 2 has a different TK inhibitor profile than erlotinib. The apoptotic effect of this compound in A549 cells was also investigated. Compound 2 induced apoptosis in A549 cells more than erlotinib. As a result of in vitro studies, it was determined that compound 2 exerts its cytotoxic and apoptotic effects on A549 cell line through multiple TK inhibition.