Abstract:
The increasing resistance of bacteria to antibacterial therapy poses an enormous health
problem, it renders the development of new antibacterial agents with novel mechanism of
action an urgent need. Peptide deformylase, a metalloenzyme which catalytically removes Nformyl group from N-terminal methionine of newly synthesized polypeptides, is an important
target in antibacterial drug discovery.
In this study, we reported the structure-based virtual screening of ZINC database in
order to discover potential hits as bacterial peptide deformylase enzyme inhibitors with more
affinity as compared to GSK1322322, previously known inhibitor.
After virtual screening, fifteen compounds of the top hits predicted were purchased and
evaluated in vitro for their antibacterial activities against two Gram positive (Staphylococcus
aureus and Enterococcus faecalis) and three Gram negative (Escherichia coli, Pseudomonas
aeruginosa and Klebsiella pneumoniae) bacteria in different concentrations by disc diffusion
method. Out of these, three compounds, ZINC00039650, ZINC03872971 and
ZINC00126407, exhibited significant zone of inhibition. The results obtained were confirmed
using the dilution method.
At the end of this study, we propose these three compounds as new and more efficient
antibacterial agents.
