Background:
The great emergence of multi-resistant bacterial strains and the low renewal
of antibiotics molecules are leading human and veterinary medicine to certain therapeutic
impasses. Therefore, there is an urgent need to find new therapeutic alternatives including new
molecules in the current treatments of infectious diseases. Methionine aminopeptidase (MetAP) is a
promising target for developing new antibiotics because it is essential for bacterial survival.
Objective:
To screen for potential MetAP inhibitors by in silico virtual screening of the ZINC database
and evaluate the best potential lead molecules by in vitro studies.
Methods:
We have considered 200,000 compounds from the ZINC database for virtual screening with
FlexX software to identify potential inhibitors against bacterial MetAP. Nine chemical compounds of
the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each inhibitor
of MetAP was tested by the disc-diffusion assay against one Gram-positive (Staphylococcus aureus)
and two Gram-negative (Escherichia coli & Pseudomonas aeruginosa) bacteria. Among the studied
compounds, compounds ZINC04785369 and ZINC03307916 showed promising antibacterial activity.
To further characterize their efficacy, the minimum inhibitory concentration was determined for
each compound by the microdilution method which showed significant results.
Results:
These results suggest compounds ZINC04785369 and ZINC03307916 as promising molecules
for developing MetAP inhibitors.
Conclusion:
Furthermore, they could therefore serve as lead molecules for further chemical modifications
to obtain clinically useful antibacterial agents.
