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

Novel benzimidazothiazole–thiazole hybrids are synthesized and evaluated for anticancer activity against HCT-116 colon cancer cells. Compound 16b shows superior cytotoxicity over doxorubicin. Molecular docking confirms strong binding to 6MTU protein, and ADMET profiling indicates favorable pharmacokinetics and low toxicity. The results highlight promising lead candidates for colon cancer drug development.

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.

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