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. (C) 2014 Elsevier Ltd. All rights reserved.

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;Bonaccorso, Carmela;Caltabiano, Gianluigi;Musumarra, Giuseppe;
2014

Abstract

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. (C) 2014 Elsevier Ltd. All rights reserved.
Antibiotics
Drug design
Enantiomers
Linezolid
Multidrug-resistant bacteria
Acetamides
Anti-Bacterial Agents
Binding Sites
Cell Survival
Drug Resistance, Multiple, Bacterial
Gram-Positive Bacteria
Hep G2 Cells
Humans
Linezolid
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Molecular Conformation
Molecular Docking Simulation
Nucleic Acid Conformation
Oxadiazoles
Oxazolidinones
RNA, Ribosomal, 23S
Staphylococcus aureus
Stereoisomerism
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/541723
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