Abstract
Antimicrobial compounds incorporating oxazolidinone and quinolone pharmacophore substructures have been synthesized and evaluated. Representative analogues 2, 5, and 6 display an improved potency versus linezolid against gram-positive and fastidious gram-negative pathogens. The compounds are also active against linezolid- and ciprofloxacin-resistant Staphylococcus aureus and Enterococcus faecium strains. The MOA for these new antimicrobials is consistent with a combination of protein synthesis and gyrase A/topoisomerase IV inhibition, with a structure-dependent degree of the contribution from each inhibitory mechanism.
MeSH terms
-
Acetamides / pharmacology
-
Anti-Bacterial Agents / chemical synthesis*
-
Anti-Bacterial Agents / chemistry
-
Anti-Bacterial Agents / pharmacology*
-
Ciprofloxacin / pharmacology
-
DNA Topoisomerase IV / antagonists & inhibitors
-
Drug Resistance, Bacterial
-
Gram-Negative Bacteria / drug effects
-
Gram-Positive Bacteria / drug effects
-
Linezolid
-
Microbial Sensitivity Tests
-
Molecular Structure
-
Oxazolidinones / chemical synthesis*
-
Oxazolidinones / chemistry
-
Oxazolidinones / pharmacology*
-
Quinolones / chemical synthesis*
-
Quinolones / chemistry
-
Quinolones / pharmacology*
-
Structure-Activity Relationship
Substances
-
Acetamides
-
Anti-Bacterial Agents
-
Oxazolidinones
-
Quinolones
-
Ciprofloxacin
-
DNA Topoisomerase IV
-
Linezolid