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

• 1,3-Thiazole hybrids serve as key scaffolds in drug discovery due to their diverse biological properties. • Efficient synthesis of pyridine and 1,3,4-oxadiazole-conjugated 1,3-thiazole hybrids. • In vitro anticancer activity against the MCF-7 breast cancer cell line using the Sulforhodamine B (SRB) assay. • Molecular docking studies (PDB ID: 3ERT ) to predict favourable binding interactions and orientations within the active site of the target protein. • Molecular dynamics and MM-GBSA analyses to confirm the stability and binding affinity of compounds 7a–h , • DFT studies to find out the energy gaps, reactivity, and stability of compounds 7a-h . • Evaluation of drug-likeness to assess the pharmacokinetic potential of the synthesized hybrids, in agreement with Lipinski’s and Jorgensen’s rules. • Detailed SAR study highlighting the influence of functional groups on the cytotoxic potential of the 1,3-thiazole hybrids. 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.