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 an antibacterial 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

Fortuna, C., Bonaccorso, C., Bulbarelli, A., Caltabiano, G., Rizzi, L., Goracci, L., et al. (2013). New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 65, 533-545 [10.1016/j.ejmech.2013.03.069].

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

BULBARELLI, ALESSANDRA;RIZZI, LAURA;COCUZZA, CLEMENTINA ELVEZIA;MUSUMECI, ROSARIO
2013-07

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 an antibacterial 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
Si
Articolo in rivista - Articolo scientifico
Oxazolidinones; Linezolid; Drug design; Antimicrobial activity; Cell viability; Staphylococcus aureus
English
533
545
13
Fortuna, C., Bonaccorso, C., Bulbarelli, A., Caltabiano, G., Rizzi, L., Goracci, L., et al. (2013). New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 65, 533-545 [10.1016/j.ejmech.2013.03.069].
Fortuna, C; Bonaccorso, C; Bulbarelli, A; Caltabiano, G; Rizzi, L; Goracci, L; Musumarra, G; Pace, A; Palumbo Piccionello, A; Guarcello, A; Pierro, P; Cocuzza, C; Musumeci, R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/44991
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