Activity of non-fluorinated quinolones (NFQs) against quinolone-resistant Escherichia coli and Streptococcus pneumoniae
The newly developed 8-methoxy, non-fluorinated quinolones (NFQs) were studied to elucidate their enzyme inhibitory activity against wild-type and mutant GyrA (Ser-83→Trp) forms of Escherichia coli DNA gyrase. Using a DNA supercoiling inhibition assay, the NFQs were found to inhibit 50% (IC50) of the...
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Published in | Journal of antimicrobial chemotherapy Vol. 48; no. 1; pp. 29 - 36 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
01.07.2001
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | The newly developed 8-methoxy, non-fluorinated quinolones (NFQs) were studied to elucidate their enzyme inhibitory activity against wild-type and mutant GyrA (Ser-83→Trp) forms of Escherichia coli DNA gyrase. Using a DNA supercoiling inhibition assay, the NFQs were found to inhibit 50% (IC50) of the E. coli DNA gyrase activity in the 1.6–3.2 mg/L concentration range and were comparable to ciprofloxacin. However, against the GyrA (Ser-83→Trp) mutant, the NFQs were ~16-fold more potent than ciprofloxacin. Antibacterial potency of the NFQs was investigated using clinical isolates of E. coli and penicillin-resistant Streptococcus pneumoniae (PRSP), including strains with reduced susceptibility to quinolones. Against 20 uncharacterized clinical isolates of E. coli, the MIC90s of the NFQs were in the 0.125–0.25 mg/L range while those of ciprofloxacin, trovafloxacin, gatifloxacin and clinafloxacin were in the 0.016–0.125 mg/L range. Against clinical isolates with characterized mutations in gyrA and parC, PGE9262932, an NFQ, was two- to eight-fold more potent than ciprofloxacin. Against 23 clinical isolates of PRSP, the NFQs (MIC90 0.031–0.125 mg/L) were more potent than ciprofloxacin, trovafloxacin, and gatifloxacin (MIC90 0.25–2.0 mg/L), and at least as potent as clinafloxacin (MIC90 0.125 mg/L). Against S. pneumoniae strains with gyrA and parC mutations, the NFQs (MIC 0.125–1.0 mg/L) were more potent than ciprofloxacin, trovafloxacin and gatifloxacin (MIC 4–32 mg/L), and comparable to clinafloxacin (MIC 0.5–1 mg/L). |
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Bibliography: | istex:88E95846FD2776B334CD0BC3A707751E690364DE PII:1460-2091 ark:/67375/HXZ-N3X4DRF2-C local:0480029 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0305-7453 1460-2091 1460-2091 |
DOI: | 10.1093/jac/48.1.29 |