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 pharmacophore-constrained
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.
