The Suppressive Effect of Novel Hydrazones-Tethered Imidazoles in HCT-116 and HT-29 Colorectal Cancer Cells in a Time-Dependent Manner

Abstract

Molecular hybridization is an effective method for developing new therapeutic compounds. The combination of the imidazole ring from numerous FDA-approved anticancer drugs and the hydrazone moiety, which has been extensively studied and demonstrated to possess a diverse range of pharmacological properties led to the development of a group of hybrid compounds. Synthesized compounds were characterized by various spectral techniques including FTIR, 1H-NMR, 13C-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 anticancer activity especially HRK-1, HRK-5 and HRK-7 with IC50 values of 5 μM. 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 modelling 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.

Note:
Funding Declaration: The authors express a debt of gratitude to Erciyes University's Research Foundation (Grant No: FDK-2021-10470).

Conflicts of Interest: The authors declared no potential conflicts of interest.

Keywords: Imidazole, Hydrazone, Colon cancer, Molecular hybridization, Apoptosis, Molecular modeling