The Suppressive Effect of Novel Hydrazones-Tethered Imidazoles in HCT-116 and HT-29 Colorectal Cancer Cells: Synthesis, Biological Activity and Molecular Modeling Studies

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Abstract A series of hybrid compounds containing both the imidazole ring and the hydrazone moiety have been synthesized. Synthesized compounds were characterized by various spectral techniques, including FT‐IR, 1 H‐NMR, 13 C‐NMR, and HRMS. The compounds were evaluated for their antiproliferative activities on colorectal cancer cells HCT‐116 and HT‐29 in a time‐dependent manner. Among them, some compounds exhibited remarkable anti‐cancer activity with a less cytotoxic effect on non‐cancerous cell lines, especially HRK‐2 with IC 50 value of 1.35±0.18 μM in HCT‐116 cells and HRK‐5 with IC 50 value of 2.67±0.61 μM in HT‐29 cells. Investigations of colon cancer cell death were performed, and the most active compounds were found to trigger cell death via nuclear localization and induce S phase arrest of the colon cancer cell. Moreover, molecular modeling studies for the synthesized compounds was performed to predict their binding affinities toward the active site of BCL‐2. The findings of the molecular modeling investigations were highly consistent with those of the cytotoxicity results.