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.
Keywords:
Antibiotics; Drug design; Enantiomers; Linezolid; Multidrug-resistant bacteria.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / chemistry*
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Acetamides / pharmacology
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Binding Sites
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Cell Survival / drug effects
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Drug Resistance, Multiple, Bacterial / drug effects
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Gram-Positive Bacteria / drug effects
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Gram-Positive Bacteria / genetics
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Hep G2 Cells
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Humans
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Linezolid
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Methicillin-Resistant Staphylococcus aureus / drug effects
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Microbial Sensitivity Tests
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Molecular Conformation
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Molecular Docking Simulation
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Nucleic Acid Conformation
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Oxadiazoles / chemical synthesis
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Oxadiazoles / chemistry*
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Oxadiazoles / pharmacology
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Oxazolidinones / chemistry*
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Oxazolidinones / pharmacology
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RNA, Ribosomal, 23S / chemistry
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RNA, Ribosomal, 23S / genetics
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Staphylococcus aureus / drug effects
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Stereoisomerism
Substances
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Acetamides
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Anti-Bacterial Agents
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Oxadiazoles
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Oxazolidinones
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RNA, Ribosomal, 23S
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Linezolid