Recherche de nouvelles molécules bioactives par criblage virtuel et applications à l’inhibition de la peptide déformylase.

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.