title: Grepafloxacin, a dimethyl derivative of ciprofloxacin, acts preferentially through gyrase in Streptococcus pneumoniae: role of the C-5 group in target specificity.
abstract: Grepafloxacin, a 5-methyl-7-piperazinyl-3"-methyl analogue of ciprofloxacin, was used to obtain stepwise-selected mutants of Streptococcus pneumoniae 7785. Analysis of the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes in these mutants revealed that gyrA mutations preceded those in parC. Given that ciprofloxacin (5-H,7-piperazinyl) and AM-1121 (5-H,7-piperazinyl-3"-methyl) both act through topoisomerase IV, we conclude that the 5-methyl group of grepafloxacin favors gyrase in S. pneumoniae.
authors.affiliation: Molecular Genetics Group, Department of Biochemistry and Immunology, St. George's Hospital Medical School, University of London, London SW17 0RE, United Kingdom.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Morris
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Pan
authors.forename: L Mark
authors.initials: LM
authors.lastname: Fisher
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000031:analogs & derivatives; D027081:DNA Gyrase / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems; D024841:Fluoroquinolones; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D002939:Ciprofloxacin; D027081:DNA Gyrase; C075375:grepafloxacin