Structure-activity relationship of fluoroquinolone in Escherichia coli.
Structure-activity relationship of 20 fluoroquinolones was studied using the susceptible and 4 resistant Escherichia coli which were developed against 4 fluoroquinolones [ciprofloxacin (1), KR-10755 (6), norfloxacin (2), and ofloxacin (3)] in our laboratory. The C-7 and C-8 substituents of fluoroquinolone were important in various functions such as the inhibitory activity on DNA gyrase, permeability, and efflux. Among 20 fluoroquinolones, compounds with a 3-methyl-3,7-diazabicyclo[3.3.0]octan-1(5)-ene-7-yl substituent at the C-7 position or a chlorine substituent at the C-8 position showed a good inhibitory activity on DNA gyrase (especially a mutated DNA gyrase). Compounds with a 3,7-diazabicyclo [3.3.0]octan-1(5)-ene-7-yl substituent at the C-7 position showed good permeability in the susceptible and resistant strains, while compounds with a fluorine substituent at the C-8 position were less effluxed from cells.
Lee
S
S
Dept. of Biology, Seoul Women's University, Korea.
Park
T
T
Lee
Y
Y
D000890:Anti-Infective Agents / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D024841:Fluoroquinolones; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D007202:Indicators and Reagents