Virtual Screening Approach of Bacterial Peptide Deformylase Inhibitors Results in New Antibiotics

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 N-formyl group from N-terminal methionine of newly synthesized polypeptides, is an important target in antibacterial drug discovery. In this study, we report 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 one Gram positive (Staphylococcus aureus) 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. Thus, these proposed compounds may aid the development of more efficient antibacterial agents.

Romanian Bee Product Analysis: Chemical Composition, Antimicrobial Activity, and Molecular Docking Insights

“…The interaction profile of the compounds docked with peptide deformylase showed an excellent fit of epicatechin, ferulic acid, gallic acid, and rosmarinic acid in the binding pocket of the protein, GLN50, GLU133, GLY81, LEU91, GLN65, LEU112, VAL50, and GLY110 (Figure 2). A similar observation was made by Merzoug et al (2017) [103]. Other studies by [104,105] found compounds with hydroxamate functional groups to be viable antibacterial agents when targeting the peptide deformylase protein.…”

Quercetin, a secondary metabolite present in methanolic extract of Calendula officinalis, is a potent inhibitor of peptide deformylase, undecaprenyl pyrophosphate synthase and DNA primase enzymes of Staphylococcus aureus: an in vitro and in silico result analysis

“…Virtual screening like docking and simulation are fast and cheap methods that give sufficient primary information of inhibition pathway of phytochemicals against essential enzymes of various pathogens. 40 Further, in silico structure based drug designing can be used to improve the efficacy of inhibitory effects of Quercetin like natural molecules. This study unbolts the opportunity for further research on these types of natural compounds, as it is evident from the facts that these compounds have great potential to be used as lead molecules in future development of drugs.…”

Screening of anti‐ Vibrio activity of marine fungal methanolic fractions to control vibriosis in white shrimp ( Litopenaeus vannamei )

“…In screening for potential antimicrobial agents, most researchers used paper disc diffusion method (Diánez et al, 2018; Kelebek et al, 2017; Merzoug et al, 2018) and broth microdilution method (Romulo et al, 2018; Thielmann et al, 2019; Yousfi et al, 2020). The paper disc diffusion method may be labour consuming and require significant quantities of the test materials.…”