活动trovafloxacin相比其他氟喹诺酮类原料药对纯化拓扑异构酶和gyrA grlA金黄色葡萄球菌的突变体。

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Gootz TD, Zaniewski RP, Haskell SL Kaczmarek FS,莫里斯AE

活动trovafloxacin相比其他氟喹诺酮类原料药对纯化拓扑异构酶和gyrA grlA金黄色葡萄球菌的突变体。

Antimicrob代理Chemother。1999年8月,43 (8):1845 - 55。

PubMed ID

10428901 (在PubMed

]

文摘

频率的突变与trovafloxacin阻力和其他四个喹诺酮测定与quinolone-susceptible金黄色葡萄球菌RN4220直接电镀法。第一步选择突变体与trovafloxacin较少(1.1 x 10 (-10) 2 - 4 x麦克风)比与左氧氟沙星和环丙沙星(3.0 x 10 (7) - 3.0 x 10(8)在2到4 x麦克风)。突变体与改变GrlA (Ser80 - - >板式换热器或酪氨酸)是最常见的选择与trovafloxacin、环丙沙星、左氧氟沙星或pefloxacin。第一步突变体与sparfloxacin很难选择;然而,第二次突变体的突变gyrA很容易选择当一个先前存在的突变grlA在场。对29个金黄色葡萄球菌临床分离株与已知突变gyrA和/或grlA, trovafloxacin是最活跃的喹诺酮测试(麦克风,50%的隔离是抑制(麦克风(50))和麦克风(90),1和4 microg /毫升,分别);相比之下,麦克风(50)和麦克风(90)年代是32和128,16和32,8 - 32岁,128年和256年为环丙沙星microg /毫升,sparfloxacin,左氧氟沙星和pefloxacin分别。与突变菌株grlA只有一般容易喹诺酮类的测试。突变体的变化grlA和gyrA麦克风都较高,一般超过环丙沙星的易感性断点,sparfloxacin,左氧氟沙星,pefloxacin。的利血平(20 microg /毫升)降低环丙沙星四倍以上的中等收入国家只有18 29个临床菌株。 Topoisomerase IV and DNA gyrase genes were cloned from S. aureus RN4220 and from two mutants with changes in GrlA (Ser80-->Phe and Glu84-->Lys). The enzymes were overexpressed in Escherichia coli GI724, purified, and used in DNA catalytic and cleavage assays that measured the relative potency of each quinolone. Trovafloxacin was at least five times more potent than ciprofloxacin, sparfloxacin, levofloxacin, or pefloxacin in stimulating topoisomerase IV-mediated DNA cleavage. While all of the quinolones were less potent in cleavage assays with the altered topoisomerase IV, trovafloxacin retained its greater potency relative to those of the other quinolones tested. The greater intrinsic potency of trovafloxacin against the lethal topoisomerase IV target in S. aureus contributes to its improved potency against clinical strains of S. aureus that are resistant to other quinolones.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Pefloxacin	DNA促旋酶亚基	蛋白质	流感嗜血杆菌(写明ATCC 51907株/ DSM 11121 / KW20 / Rd)	是的	抑制剂	细节
Trovafloxacin	DNA促旋酶亚基	蛋白质	流感嗜血杆菌(写明ATCC 51907株/ DSM 11121 / KW20 / Rd)	是的	抑制剂	细节