格帕沙星，环丙沙星的二甲基衍生物，在肺炎链球菌中主要通过拓扑异构酶起作用：C-5基团在靶点特异性中的作用。
Grepafloxacin, a dimethyl derivative of ciprofloxacin, acts preferentially through gyrase in Streptococcus pneumoniae: role of the C-5 group in target specificity.
作者信息
Morris Julia E, Pan Xiao-Su, Fisher L Mark
机构信息
Molecular Genetics Group, Department of Biochemistry and Immunology, St. George's Hospital Medical School, University of London, London SW17 0RE, United Kingdom.
出版信息
Antimicrob Agents Chemother. 2002 Feb;46(2):582-5. doi: 10.1128/AAC.46.2.582-585.2002.
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.
摘要
格帕沙星是环丙沙星的5-甲基-7-哌嗪基-3''-甲基类似物，用于获得肺炎链球菌7785的逐步选择突变体。对这些突变体中gyrA、gyrB、parC和parE基因的喹诺酮耐药决定区进行分析，结果显示gyrA突变先于parC突变。鉴于环丙沙星（5-H，7-哌嗪基）和AM-1121（5-H，7-哌嗪基-3''-甲基）均通过拓扑异构酶IV发挥作用，我们得出结论，格帕沙星的5-甲基基团有利于肺炎链球菌中的gyrase。
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Antimicrob Agents Chemother. 2001 Jun;45(6):1649-53. doi: 10.1128/AAC.45.6.1649-1653.2001.
3
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Microb Drug Resist. 2000 Winter;6(4):259-67. doi: 10.1089/mdr.2000.6.259.
4
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J Antimicrob Chemother. 2000 Apr;45 Suppl 1:101-6. doi: 10.1093/jac/45.suppl_3.101.
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J Antimicrob Chemother. 2000 May;45(5):583-90. doi: 10.1093/jac/45.5.583.
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8
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