Green One-Pot Synthesis of Thiazole Scaffolds Catalyzed by Reusable NiFeO Nanoparticles: Binding Affinity and Anticancer Activity Studies.

A facile, green, one-pot multicomponent synthesis strategy was employed to fabricate novel thiazole scaffolds incorporating phthalazine, pyridazine, and pyrido-pyridazine derivatives (-). This synthetic route entailed the reaction of an α-halo carbonyl compound () with thiosemicarbazide () and various anhydrides (-), utilizing NiFeO nanoparticles as a reusable catalyst in an ethanol:water (1:1) solvent system. The cytotoxicity of the synthesized compounds was meticulously assessed against three cancer cell lines, A375, HeLa, and MCF-7, employing IC values (μM) as the benchmark, and compared to the reference drug erlotinib. Compound displayed remarkable efficacy against A375 (0.87 ± 0.31 μM), HeLa (1.38 ± 1.24 μM), and MCF-7 (1.13 ± 0.96 μM) cell lines, significantly surpassing erlotinib's IC values. Additionally, compounds , , , and demonstrated notable cytotoxicity across all tested cell lines, indicating their potential as effective anticancer agents. docking studies against Hsp82 and Hsp90 proteins indicated that ligands , , , , , and had superior binding affinities compared to erlotinib. ADME analysis showed that compounds , , , , and had favorable pharmacokinetic profiles, including nontoxicity, high human intestinal absorption, and low CYP inhibitory promiscuity. Structure-activity relationship analysis revealed that cyano and benzylidene substitutions significantly enhanced anticancer activity. Overall, the synthesized compounds, particularly , demonstrated high efficacy, favorable binding interactions, and promising pharmacokinetic profiles, making them strong candidates for further development as anticancer agents.