Synthesis, characterization, and in vitro investigation of antiproliferative activity of new compounds containing thymol nuclei

Thymol is a plant secondary metabolite that has been the subject of numerous investigations in pharmaceutical and medicinal chemistry due to its wide range of biological activities. Scientists have synthesized various derivatives of thymol, studied their effects against many diseases and pathogens, and obtained promising results. This thesis aimed to understand the effects of thymol derivatives against cancer cells and to develop new anticancer drug candidates. Twelve new imine compounds were synthesized by the condensation of 6-aminothymol with various aldehydes, characterized by spectroscopic methods, and their antiproliferative effects were evaluated against HepG2 (liver), DLD-1 (colorectal), MCF-7 (breast), and A549 (lung) cancer cell lines. Cisplatin and paclitaxel were used as positive control, and the selectivity of the compounds on healthy cells was assessed using the HEK-293T cell line. According to the findings, the synthesized compound 4f ((E)-4-(3-(tert-butyl)-2-hydroxybenzylideneamino)-2-isopropyl-5-methylphenol) exhibited the strongest effect with low IC50 values and high selectivity in HepG2 and DLD-1 cell lines. Similarly, compound 4k ((E)-4-(anthracen-9-ylmethyleneamino)-2-isopropyl-5-methylphenol) showed potent effects in the DLD-1 and MCF-7 cell lines. Additionally, 4i ((E)-4-(4-(diethylamino)-2-hydroxybenzylideneamino)-2-isopropyl-5-methylphenol) was another effective compound in the HepG2 cell line. Compound 4l ((E)-4-(3-bromo-5-chlorobenzylideneamino)-2-isopropyl-5-methylphenol) demonstrated significant anticancer activity in the MCF-7 cell line, indicating its potential as a candidate for drug development targeting breast cancer. On the other hand, compounds 4b ((E)-2-isopropyl-5-methyl-4-((5-methylthiophen-2-yl)methyleneamino)phenol), 4d ((E)-4-(5-fluoro-2-hydroxybenzylideneamino)-2-isopropyl-5-methylphenol), 4e ((E)-4-(2-hydroxy-5-methoxybenzylideneamino)-2-isopropyl-5-methylphenol), and 4j ((E)-4-(5-bromo-2-hydroxybenzylideneamino)-2-isopropyl-5-methylphenol) displayed reasonable cytotoxicity against cancer cells but also caused higher than expected toxicity in healthy cells, suggesting the need for further optimization of these compounds.