Novel Benzimidazole-Based Compounds as Antimicrobials: Synthesis, Molecular Docking, Molecular Dynamics and in silico ADME Profile Studies


YEŞİLÇAYIR E., ÇELİK İ. , Şen H. T. , Gürpınar S. S. , ERYILMAZ M., Kilcigil G.

Acta chimica Slovenica, vol.69, no.2, pp.419-429, 2022 (Journal Indexed in SCI Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 69 Issue: 2
  • Publication Date: 2022
  • Doi Number: 10.17344/acsi.2021.7314
  • Title of Journal : Acta chimica Slovenica
  • Page Numbers: pp.419-429
  • Keywords: antimicrobial activity, Benzimidazole, molecular docking, molecular dynamics

Abstract

Some novel benzimidazole derivatives were synthesized and their antimicrobial activities were evaluated. Compounds 3a and 3b exhibited excellent antibacterial activity with MIC values <4 µg/mL against Staphylococcus aureus ATCC 29213 (MSSA) and Staphylococcus aureus ATCC 43300 (MRSA). Molecular docking analyzes of compounds with MIC values of 16 µg/mL and below against gram-positive bacteria and fungi were performed using FabH (β-ketoacyl-acyl carrier protein synthase III) as bacterial protein and CYP51 (sterol 14α-demethylase) as the fungal target protein. According to the molecular docking analysis, it was calculated that sufficient protein-ligand interaction energy was liberated between the compounds 2f, 3a, 3b, 3e and 3h and the antibacterial target protein FabH and strong interactions were formed between 2f and 3h and the antifungal target protein. According to RMSD, RMSF and MMPBSA measurements obtained from molecular dynamics, it is understood that compounds 3a and 3b maintain protein-ligand stability in silico physiological conditions.