Synthesis, Molecular Docking, and Anticancer Activity of New Thiophene Linked 1,2,4-Triazolo[4,3-b]pyridazine Derivatives Against the MCF-7 Human Breast Carcinoma Cell Line

In order to develop compounds with anticancer potential, a novel series of 3-aryl-6-(thiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazine derivatives was synthesized. The synthesis was carried out via the use of environmentally benign hypervalent iodine reagent in aqueous media. The SRB assay was employed for the evaluation of anti-cancer potential against MCF-7 carcinoma cell line. Compounds with furan and 2,5-dimethoxyphenyl substituents at the triazole ring showed admirable anticancer potential with GI₅₀ value less than 10 μg/mL. Compounds with 2-chlorophenyl, 3,4-dimethoxyphenyl, 4-methylphenyl and 4-isopropylphenyl substituents showed moderate potential with GI₅₀ values of 14, 54, 77, and 51 respectively. The two most active compounds were further studied via molecular docking against six proteins (PDB ID: 1E31, 1FDW, 1M17, 2W3L, 5GWK, and 6CBZ). The calculated binding energies and interactions in silico studies indicated the synthesized compounds to be potential EGFR inhibitor. Overall, this study highlighted the potential of the newly prepared analogues as promising leads for further development.