Thomas A, Tocher J, Edwards D I
Chemotherapy Research Unit, Polytechnic of East London, UK.
J Antimicrob Chemother. 1990 May;25(5):733-44. doi: 10.1093/jac/25.5.733.
The object of this study was to determine whether 4-quinolone antimicrobials were reduced under biologically attainable redox conditions and whether they had any effect on DNA in the absence of the DNA gyrase enzyme. Electrochemical characteristics of the drugs were investigated using d c polarography, differential pulse polarography and cyclic voltammetry. The ability of the drugs to interact with, and cause damage to, naked DNA was investigated by a phi X174 DNA double transfection assay. Induction of DNA SOS repair was assessed using a stain of Escherichia coli in which the synthesis of beta-galactosidase was under the control of the su1A gene. Growth studies were performed using a conductimetric method in a Malthus system. All five 4-quinolones examined had redox potentials lower (more negative) than -1.2 V and thus were incapable of being reduced in biological systems, even under strict anaerobiosis. Exposure of all drugs to single-stranded phi X174 DNA for up to 50 h engendered no detectable damage. However, all the drugs induced DNA SOS repair, in the order ciprofloxacin greater than fleroxacin = pefloxacin greater than norfloxacin greater than nalidixic acid. This rank order corresponds approximately with antibacterial efficiency. The growth studies indicated that redoxyendonuclease III and excision repair enzymes may be involved in the fixation of quinolone-induced damage.
本研究的目的是确定4-喹诺酮类抗菌药物在生物可达到的氧化还原条件下是否会被还原，以及在没有DNA促旋酶的情况下它们对DNA是否有任何影响。使用直流极谱法、微分脉冲极谱法和循环伏安法研究了这些药物的电化学特性。通过φX174 DNA双转染试验研究了药物与裸露DNA相互作用并对其造成损伤的能力。使用一种大肠杆菌菌株评估DNA SOS修复的诱导情况，在该菌株中β-半乳糖苷酶的合成受su1A基因控制。在马尔萨斯系统中使用电导法进行生长研究。所检测的所有五种4-喹诺酮类药物的氧化还原电位均低于（更负）-1.2 V，因此即使在严格厌氧条件下也无法在生物系统中被还原。将所有药物暴露于单链φX174 DNA长达50小时，未产生可检测到的损伤。然而，所有药物均诱导了DNA SOS修复，其顺序为环丙沙星＞氟罗沙星 = 培氟沙星＞诺氟沙星＞萘啶酸。这个排序大致与抗菌效率相对应。生长研究表明，氧化还原内切酶III和切除修复酶可能参与喹诺酮类药物诱导损伤的修复。
