Developing effective antimicrobial agents: synthesis and molecular docking study of ciprofloxacin-benzimidazole hybrids

Abstract

In this study, we designed and synthesized some new ciprofloxacin-benzimidazole hybrid compounds and evaluated them for their antimicrobial activity against four Gram-positive (B. subtilis, B. megaterium, E. faecalis and S. aureus) and five Gram-negative (E. coli, E. cloacae, P. aeruginosa, S. typhimurium and Y. pseudotuberculosis) bacteria. Most of the synthesized compounds were found to show better or equivalent activities when compared with the standard drug ciprofloxacin. Among the tested compounds, compounds 4 v and 4 w showed more or the same activities against most of the bacteria. In the light of the information obtained from this study, the results showed that the synthesized hybrid compounds could be potential antibiotic agents. Antimicrobial activities were also confirmed by molecular docking studies against active site of Staphylococcus aureus DNA gyrase. Based on docking results, the compound 4e-protein complex having the best score was used to perform 100 ns MD simulations to analyze the dynamic behavior and stability of the complex. Furthermore, the active compounds demonstrated acceptable ranges of ADMET properties such as partition coefficients, cellular permeability, and toxicity values.

A series of some new ciprofloxacin-benzimidazole hybrids were synthesized and investigated for their antimicrobial activities against Gram-positive and Gram-negative bacteria. Most of the synthesized compounds were found to show better or equivalent activities when compared with the standard drug ciprofloxacin. Results were confirmed by a molecular docking study against S. aureus DNA gyrase. Also, ADMET properties were also calculated. These were found to be within an acceptable range of 95 % drug molecules.image