Investigation of the In Vitro and In Silico Anticancer Potential of Novel 4-Arylthiazole-Hydrazone Derivatives.

The anticancer efficacy of 4-aryl-2-hydrazinothiazole derivatives, which combine a thiazole known for its wide range of medicinal applications and a hydrazide/hydrazone structure known for its unique biological properties, has been determined in numerous studies. In this study, novel 2-[4-[(2-(4-substituted thiazol-2-yl)hydrazono)methyl]phenoxy]acetic acid derivatives (2a-l) were synthesized and evaluated for their anticancer activity in MCF-7 breast cancer, A549 lung cancer, and L929 normal cell lines using cytotoxicity, apoptosis, and caspase-3 activation assays. The compounds were found to exhibit high cytotoxicity, particularly showing more selective and high-potential antiproliferative activity on the MCF-7 cell line. In apoptosis studies, compounds 2c, 2d, and 2h caused programmed cell death in MCF-7 cells exceeding 24%, close to cisplatin. Among these compounds, the derivative 2c containing 4-methoxyphenyl caused caspase-3 activation at a level similar to cisplatin. To conduct in silico studies of the compounds, molecular docking studies with the (4QTX) caspase-3 enzyme, molecular dynamics simulation for three compounds (2d, 2g and 2l), and Density Functional Theory (DFT) studies were performed. These studies have shown that the carboxylate groups in the compounds form strong and stable interactions with Arg64 and Arg207.