Computer-aided discovery of antimicrobial agents as potential enoyl acyl carrier protein reductase inhibitors

Abstract

Purpose: To perform a virtual screening for a set of drug-like ligand library against the Staphylococcus aureus enoyl acyl carrier protein reductase, saFabI. Methods: The virtual screening was conducted based on a previously validated pharmacophoreconstrained docking. Consequently, the top list obtained was filtered using visual inspection where forty compounds were selected for experimental testing using disk-diffusion test and broth dilution method. The hits obtained were checked for their toxicity against human fibroblasts cell lines. Results: Three compounds were active against Staphylococcus aureus and other tested gram-positive bacteria. However, no significant inhibitory activity (p < 0.05) was detected against Escherichia coli or Candida albicans. The minimum inhibitory concentration (MIC) values for the most active compounds were identified using the broth dilution method; all of them exhibited inhibitory activity within micromolar range.The docking results showed that the hits obtained exhibited a small size with a nice binding mode to saFabI enzyme, forming the important interactions with the key residues. Furthermore, the best three hits demonstrated good safety profile as they did not show any significant toxicity against human fibroblast cell line. Conclusion: Overall, the newly discovered hits can act as a good starting point in the future for the development of safe and potent antibacterial agents.