The synthesis and the in vitro antibacterial activity of novel Linezolid-like oxadiazoles is reported. Replacement of the Linezolid morpholine C-ring with 1,2,4-oxadiazole results in a bacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of Linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding pose of the newly synthesized compounds as compared with the crystallographic pose of Linezolid, the 1,2,4-oxadiazole moiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interaction with U2585 is retained.

New Linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens

FORTUNA, COSIMO GIANLUCA;BONACCORSO, CARMELA;MUSUMARRA, Giuseppe;
2013-01-01

Abstract

The synthesis and the in vitro antibacterial activity of novel Linezolid-like oxadiazoles is reported. Replacement of the Linezolid morpholine C-ring with 1,2,4-oxadiazole results in a bacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of Linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding pose of the newly synthesized compounds as compared with the crystallographic pose of Linezolid, the 1,2,4-oxadiazole moiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interaction with U2585 is retained.
2013
Oxazolidinones; Linezolid; Drug design
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/42584
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