Comparison of in vitro activities of fluoroquinolone-like 2,4- and 1,3-diones.
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.
Oppegard
Lisa M
LM
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Streck
Kathryn R
KR
Rosen
Jonathan D
JD
Schwanz
Heidi A
HA
Drlica
Karl
K
Kerns
Robert J
RJ
Hiasa
Hiroshi
H
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
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D014764:Viral Proteins; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase
J Biol Chem. 2000 Nov 3;275(44):34780-6
11053451
Antimicrob Agents Chemother. 2000 Aug;44(8):2160-5
10898691
Antimicrob Agents Chemother. 2009 May;53(5):2110-9
19273673
Antimicrob Agents Chemother. 1998 Nov;42(11):2810-6
9797208
Clin Infect Dis. 1997 Jan;24 Suppl 1:S17-8
8994777
J Biol Chem. 1993 Nov 15;268(32):24481-90
8227000
Antimicrob Agents Chemother. 2002 Nov;46(11):3370-80
12384338
Antimicrob Agents Chemother. 1999 Dec;43(12):2969-74
10582891
J Biol Chem. 2003 Mar 7;278(10):8861-8
12511566
Antimicrob Agents Chemother. 1996 Dec;40(12):2714-20
9124828
Antimicrob Agents Chemother. 1997 Feb;41(2):471-4
9021211
Antimicrob Agents Chemother. 2007 Apr;51(4):1191-201
17261623
Methods Enzymol. 1993;217:270-9
8474334
Tetrahedron Lett. 2009 Feb 18;50(7):785-789
20160840
J Biol Chem. 1994 Jan 21;269(3):2093-9
8294462
Antimicrob Agents Chemother. 1998 Nov;42(11):2978-84
9797236
Expert Rev Anti Infect Ther. 2003 Oct;1(3):363-70
15482134
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13991-6
9391140
J Med Chem. 2006 Nov 2;49(22):6435-8
17064062
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11801-5
8524852
Mol Microbiol. 1994 Aug;13(4):641-53
7997176
Science. 2008 Jul 18;321(5887):356-61
18635788
Antimicrob Agents Chemother. 2005 May;49(5):1949-56
15855518
Science. 2009 Aug 28;325(5944):1089-93
19713519
Antimicrob Agents Chemother. 2008 Nov;52(11):3915-21
18765690
J Antimicrob Chemother. 2008 Jul;62(1):98-104
18390884
J Bacteriol. 1979 Nov;140(2):424-35
227840
Curr Top Med Chem. 2009;9(11):981-98
19747119
Antimicrob Agents Chemother. 2009 Sep;53(9):3822-31
19564360
Biochemistry. 2002 Oct 1;41(39):11779-85
12269820