The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported.Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activityagainst Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or evensuperior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) sidechainare required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity butits presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using twodifferent approaches e FLAP and Amber software e shows that in the binding pose of the newly synthesizedcompounds as compared with the crystallographic pose of linezolid, the 1,2,4-oxadiazolemoiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interactionwith U2585 is retained.
- Drug Discovery
- Organic Chemistry