Synthesis, Cytotoxic Activity, Docking and MD Simulation of N,N-Disubstituted New Benzimidazolium Salts

Abstract

Novel N,N-disubstituted benzimidazolium salts were efficaciously synthesized in moderate to high yields and identified via 1H NMR and 13C NMR analyses. These compounds were tested on human liver cancer, prostate cancer, and normal embryonic kidney cell lines for 72 h. The results demonstrated that these compounds had antiproliferative activity. In particular, it was found that one of the compounds, 1-(3-chlorobenzyl)-3-(3-methylbenzyl)-1H-benzo[d]imidazol-3-ium chloride, showed very high activity against liver cancer cell line and the IC<inf>50</inf> value of this compound was almost twice as low as the IC<inf>50</inf> value of cisplatin. The anticancer activity potential of the compounds was explored through computational methods to support the experimental study results. The binding potential of the compounds to human sulfotransferase 1A1 (SULT1A1) was investigated through molecular docking and molecular dynamics simulation. Their electrochemical properties were computed via density functional theory. The molecular docking study exhibited that 1-(3-methylbenzyl)-3-(4-nitrobenzyl)-1H-benzo[d]imidazol-3-ium chloride had the highest potential to bind to SULT1A1. The molecular dynamics study showed that the synthesized compounds formed a stable complex. Furthermore, the density functional theory study exhibited that 1-(3-chlorobenzyl)-3-(4-fluorobenzyl)-1H-benzo[d]imidazol-3-ium chloride might have the highest chemical stability. © 2023 Elsevier B.V., All rights reserved.