Novel pyridine and 1,3,4-oxadiazole-linked 1,3-thiazole hybrids: Synthesis, anticancer evaluation, and computational insights

Heterocyclic scaffolds are central to drug discovery due to their diverse pharmacological properties. In this work, novel pyridine and 1,3,4-oxadiazole linked 1,3-thiazole hybrids were designed and synthesized as potential anticancer agents. Their structures were confirmed by various spectroscopic methods, and the compounds were evaluated for cytotoxicity against the MCF-7 breast cancer cell line. Among the series, compound 7a (IC₅₀ = 28.51 ± 1.70 µM) displayed the most potent activity, approaching that of cisplatin (23.44 ± 2.23 µM). Substituent effects revealed that a para-methyl group enhanced activity, whereas electron-withdrawing groups reduced potency. Computational studies (docking, MD simulations, MMGBSA, DFT, and drug-likeness predictions) further supported the experimental findings and highlighted favorable binding interactions. Overall, these results identify 1,3-thiazole hybrids as promising leads for further development in anticancer research.