Exploration of N‐Tetra‐Substituted Imidazoles as Effective Agents To Counteract Gastric Cancer Cell Viability: Synthesis and Biological Evaluation

Abstract

The tetra‐substituted imidazole offers more possibilities for modification and functionalization, allowing for fine‐tuning of the compound‘s biological activity. The substituents attached to the imidazole ring can be strategically chosen to introduce specific functional groups, steric effects, or electronic properties, thereby influencing the compound‘s overall bioactivity. An efficient one‐pot synthesis of 2,4,5‐tri and 1,2,4,5‐tetrasubstituted imidazoles was performed, which involves benzyl (1,2‐diphenylethane‐1,2‐dione), N‐methyl pyrrole‐2‐carboxaldehyde, appropriate primary amine, ammonium acetate, and iodine as a catalyst. The N‐alkylation on the imidazole was performed to introduce alkyl chains. All six synthesized compounds were purified, characterized using spectroscopic techniques, and tested against the primary Human Gingival Fibroblasts (HGFs) and AGS gastric adenocarcinoma cell line to assess their effect on cell viability. All the tested molecules displayed a low percentage of dead cells >50 μM on HGFs; compounds 1‐butyl‐2‐(1‐methyl‐1H‐pyrrol‐2‐yl)‐4,5‐diphenyl‐1H‐imidazole (5b) and 2‐(1‐methyl‐1H‐pyrrol‐2‐yl)‐1‐pentyl‐4,5‐diphenyl‐1H‐imidazole (5c) have demonstrated a remarkable ability to counteract cell viability than the other compounds, specifically on AGS cells, up to a concentration of 10 μM. This suggests that these two compounds have a higher potency in reducing the viability of AGS cells than the other tested compounds. These results align with current studies highlighting the enhanced anticancer efficacy of imidazole‐pyrrole hybrids against AGS cell line.