Synthesis and Characterization of Some New Hybrids of 2-Chloroquinoline- Benzimidazole Chalcones as Potential Antibacterial Agents

Abstract

New antimicrobial agents, developed through the combination of two active pharmacophores, have proven to be effective strategies against multi-drug-resistant microbes. This study focuses on a series of newly synthesized benzimidazole-quinoline conjugates, which have been characterized and evaluated for their antimicrobial activity. The desired benzimidazole-quinoline hybrids (5a-k) were synthesized using a multistep process with high yields (87%–94%). Antimicrobial screening revealed that several of these synthesized hybrids demonstrated significant antimicrobial potential. In particular, Gram-negative bacteria such as E. coli and P. aeruginosa showed susceptibility, resulting in a significant bactericidal effect (MBC/MIC ≤ 4) when treated with these compounds in a dose-dependent manner. Among these, compounds 5f, 5g, and 5h were identified as the most active against E. coli and P. aeruginosa, demonstrating greater zones of inhibition compared to Tetracycline. Furthermore, molecular docking and simulation studies indicated that all active compounds effectively bind to the active sites of receptor proteins, with docking scores ranging from 7 to 12 kcal/mol, comparable to those of Tetracycline. This finding was further supported by root-mean-square deviation (RMSD) calculations. Given the complexity of the Gram-negative bacterial cell wall, which restricts many synthetic drugs, these new benzimidazole-quinoline conjugates (5f-h) may serve as promising leads for further development.