Exploration of novel diazinyl–thiazole based derivatives as potential antitumor agents: synthesis, in vitro screening, and computational assessment

Antitumour drugs and antidepressants for Alzheimer's disease (AD) share similar mechanisms of action, highlighting the potential for developing compounds that can target both conditions simultaneously. This study aimed to synthesise and evaluate novel thiazole derivatives as potential dual therapeutic agents for anticancer and AD treatments. The issue addressed was the need for multifunctional compounds to combat these two complex diseases with shared biological pathways. The research involved synthesising new compounds and characterising them using spectroscopic techniques. Their in vitro anticancer activities were tested against Hepg2, MCF-7, and normal Vero cells. Furthermore, in silico studies, including molecular docking against Monoamine Oxidase-A (MAO-A) and toxicity predictions, were carried out. It was found that subtle structural modifications, such as replacing a chloro group with a bromo group, significantly affected cytotoxicity. Molecular docking indicated that the ligands interact with key amino acids of MAO-A, mimicking approved AD drugs, with ligands 5a and 7a demonstrating particularly strong binding profiles. Additionally, most ligands showed oral toxicity profiles comparable to or lower than current AD medications. These findings are significant because they provide valuable insights into designing and optimising thiazole derivatives as dual therapeutic candidates. This work offers a solid foundation for further experimental investigation and the potential development of novel clinical applications for cancer and AD. Conformational Changes of Molecule 9b upon docking into Protein 2Z5X .