Novel oxazolidinone-quinolone hybrid antimicrobials.
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.
Gordeev
Mikhail F
MF
Vicuron Pharmaceuticals Inc., 34790 Ardentech Ct., Fremont, CA 94555, USA. mgordeev@vicuron.com
Hackbarth
Corinne
C
Barbachyn
Michael R
MR
Banitt
Lee S
LS
Gage
James R
JR
Luehr
Gary W
GW
Gomez
Marcela
M
Trias
Joaquim
J
Morin
Sara E
SE
Zurenko
Gary E
GE
Parker
Christian N
CN
Evans
Jonathan M
JM
White
Richard J
RJ
Patel
Dinesh V
DV
D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D015363:Quinolones; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D000069349:Linezolid