59562-68-4Relevant articles and documents
New potent antibacterials against Gram-positive multiresistant pathogens: Effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles
Fortuna, Cosimo G.,Berardozzi, Roberto,Bonaccorso, Carmela,Caltabiano, Gianluigi,Di Bari, Lorenzo,Goracci, Laura,Guarcello, Annalisa,Pace, Andrea,Palumbo Piccionello, Antonio,Pescitelli, Gennaro,Pierro, Paola,Lonati, Elena,Bulbarelli, Alessandra,Cocuzza, Clementina E.A.,Musumarra, Giuseppe,Musumeci, Rosario
, p. 6814 - 6825 (2015/02/02)
The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistant linezolid bacterial strains was higher than that of linezolid.
New linezolid-like 1,2,4-oxadiazolesactive against Gram-positive multiresistant pathogens
Fortuna, Cosimo G.,Bonaccorso, Carmela,Bulbarelli, Alessandra,Caltabiano, Gianluigi,Rizzi, Laura,Goracci, Laura,Musumarra, Giuseppe,Pace, Andrea,Piccionello, Antonio Palumbo,Guarcello, Annalisa,Pierro, Paola,Cocuzza, Clementina E. A.,Musumeci, Rosario
, p. 533 - 545 (2013/10/01)
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 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) sidechain 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.
