Synthesis, Anticancer Evaluation, and Molecular Docking of Novel Thiazolobenzimidazole-Thiazole Hybrids as Potent Colon Cancer Inhibitors.

In this study, a series of novel benzimidazothiazole-thiazole hybrids is synthesized via the condensation of 2-(1-(3-methylbenzoimidazo[2,1-b]thiazol-2-yl)ethylidene)hydrazine-1-carbothioamide with various hydrazonoyl halides and α-halo compounds. Structural elucidation is confirmed by infrared, nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. The anticancer activities of the synthesized compounds are assessed against the HCT-116 colon carcinoma cell line using the MTT assay, where compound 16b exhibits the strongest cytotoxic effect (IC₅₀ = 4.31 ± 1.07 μM), outperforming the reference drug doxorubicin (IC₅₀ = 7.05 ± 0.49 μM). Compounds 16a, 12, and 10a also demonstrate potent activity (IC₅₀ < 7.1 μM). Molecular docking studies against the colon cancer protein target 6MTU reveal that these active compounds, especially 16b, form stable interactions through key hydrogen bonding and π-type interactions, with binding energies more favorable than doxorubicin. Additionally, in silico ADMET analysis highlights excellent absorption (up to 100%), moderate distribution, CYP450 interactions, and no predicted skin sensitization toxicity. These results position compound 16b as a promising lead molecule for further preclinical development as a targeted colon cancer therapy.