Synthesis, Docking Profiles, and Biological Insights into Selenium-NHC Adducts and Benzimidazolium Salts with...

In this research, we present the successful synthesis of benzimidazolium salts (2a-e) and their corresponding selenium-NHC adducts (3a-e), achieved with satisfactory yields ranging from 75% to 88%, and characterized using spectroscopic techniques, including NMR, FTIR, and mass spectrometry analysis. This work is the first to evaluate the antimicrobial activities and molecular docking studies of these novel compounds, shedding light on the limited enhancement provided by selenium incorporation and providing valuable insights into their enzyme inhibition mechanisms. The antimicrobial and antifungal activities of these compounds were evaluated against various bacterial and yeast strains using disk diffusion and minimum inhibitory concentration (MIC) methods. Benzimidazolium salts, particularly 2d and 2e, demonstrated superior antimicrobial efficacy against Staphylococcus aureus with inhibition zones of 26.73 mm and 18.10 mm and MIC values of 1.56 μg/mL, and against Candida albicans with inhibition zones of 18.10 mm and MIC values of 25 μg/mL and 12.5 μg/mL respectively, significantly outperforming the reference agents Ampicillin (15.33 mm inhibition zone; MIC: 25 μg/mL for S. aureus) and Caspofungin (14.30 mm inhibition zone; MIC: 25 μg/mL for C. albicans). Additionally, compounds 2d and 2e exhibited better activity against Escherichia coli with MIC values of 12.5 μg/mL compared to Ampicillin (25 μg/mL). Conversely, selenium-NHC compounds exhibited moderate to weak activity, with inhibition zones ranging from 8.35 to 11.93 mm and MIC values ranging from 100 to 800 μg/mL, and did not outperform the reference agents. To elucidate the potential mechanism of action, molecular docking studies were performed on compound 2d and its derivative 3d against three key bacterial enzymesDNA gyrase, dihydrofolate reductase (DHFR), and tyrosyl-tRNA synthetase (TyrRS)in addition to the fungal sterol 14-α-demethylase (CYP51) to assess possible antifungal interactions. The results revealed strong binding affinities for both bacterial and fungal enzymes. The compounds interact with crucial amino acids in the enzyme active sites, mirroring the interactions of native ligands. However, the presence of selenium in complex 3d did not enhance its inhibitory activity significantly compared to the salt 2d. The findings highlight the potential of benzimidazolium salts, particularly 2d and 2e, as promising therapeutic agents for microbial infections, with selenium incorporation offering limited enhancement in activity.