Antibacterial Activity of a Novel 1 , 2 , 4-Triazolo [ 4 , 3-A ] Pyrimidine Oxazolidinone against Broad Spectrum of Gram Positive Pathogens and Molecular Modeling Studies for its Interaction with Ribosome

Oxazolidinones are known to inhibit bacterial protein biosynthesis and act against a wide spectrum of Gram-positive bacteria. Herein, we report a novel investigational oxazolidinone compound 1, which showed potent in vitro activity against Staphylococcus aureus, Staphylococcus epidermidis, Vancomycin resistant enterococci (VRE), Streptococcus pneumoniae, Streptococcus pyogenes and other pathogens. The MIC of compound 1 was 0.125 μg/ml against S.aureus ATCC 25923, whereas that of linezolid was 1 μg/ml. Compound 1 showed faster inhibition of bacterial protein synthesis than Linezolid in S.aureus ATCC 25923. Molecular modeling studies indicated that compound 1 exhibited binding to the ribosome in a similar manner to that of Linezolid and Ranbezolid but with additional interactions from its triazolopyrimidine and thiophene rings which are probably responsible for its stronger in vitro activity.