title: Comparison of in vitro activities of fluoroquinolone-like 2,4- and 1,3-diones.
abstract: Bacterial resistance presents a difficult issue for fluoroquinolone treatment of bacterial infections. In previous work, we reported that 8-methoxy-quinazoline-2,4-diones are active against quinolone-resistant mutants of Escherichia coli. Here, we demonstrate the activity of a representative 8-methoxy-quinazoline-2,4-dione against quinolone-resistant gyrases. Furthermore, 8-methoxy-quinazoline-2,4-dione and other diones are shown to inhibit Staphylococcus aureus gyrase and topoisomerase IV with similar degrees of efficacy, suggesting that the diones might act as dual-targeting agents against S. aureus.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Oppegard
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Streck
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rosen
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Schwanz
authors.forename: Karl
authors.initials: K
authors.lastname: Drlica
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kerns
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiasa
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D027081:DNA Gyrase / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D014764:Viral Proteins; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase
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