Lhiaubet-Vallet Virginie, Cuquerella M Consuelo, Castell Jose V, Bosca Francisco, Miranda Miguel A
Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Valencia, Spain.
J Phys Chem B. 2007 Jun 28;111(25):7409-14. doi: 10.1021/jp070167f. Epub 2007 May 25.
A series of fluoroquinolones (FQs), including enoxacin (ENX), pefloxacin (PFX), norfloxacin (NFX), its N(4')-acetyl derivative (ANFX), ofloxacin (OFX), and rufloxacin (RFX) have been investigated to determine their potential as DNA photosensitizers via thymine cyclobutane dimer (T<>T) formation in DNA. At fluoroquinolone concentrations and light doses insufficient to produce direct single strand breaks, ENX, PFX, and NFX were able to produce T<>T dimers in DNA, revealed by enzymatic treatment with T4 endonuclease V. By contrast, ANFX, OFX, and RFX were inefficient in this assay. The absolute values of the triplet energies of ENX, PFX, NFX, ANFX, OFX, and RFX were estimated by means of laser flash photolysis, using flurbiprofen, 4-biphenylcarboxylic acid, and naproxen as energy acceptors. They were found to be 273, 269, 269, 265, 262, and 253 kJ/mol, respectively. Other triplet excited state properties of the FQs, including quantum yields and lifetimes, were also studied. All the results indicate that the threshold ET value required for a given compound to become a potential DNA photosensitizer via T<>T formation is in the range defined by the triplet energies of NFX and ANFX (265-269 kJ/mol). This provides the basis for an alert rule: any chemical (drugs, cosmetics, pesticides, etc.) with higher ET has to be considered with regard to its potential photogenotoxicity.
已经研究了一系列氟喹诺酮类药物（FQs），包括依诺沙星（ENX）、培氟沙星（PFX）、诺氟沙星（NFX）及其N(4')-乙酰衍生物（ANFX）、氧氟沙星（OFX）和芦氟沙星（RFX），以通过DNA中胸腺嘧啶环丁烷二聚体（T<>T）的形成来确定它们作为DNA光敏剂的潜力。在氟喹诺酮浓度和光剂量不足以产生直接单链断裂的情况下，ENX、PFX和NFX能够在DNA中产生T<>T二聚体，这通过用T4内切核酸酶V进行酶处理得以揭示。相比之下，ANFX、OFX和RFX在该测定中效率低下。使用氟比洛芬、4-联苯羧酸和萘普生作为能量受体，通过激光闪光光解估计了ENX、PFX、NFX、ANFX、OFX和RFX的三线态能量绝对值。发现它们分别为273、269、269、265、262和253 kJ/mol。还研究了氟喹诺酮类药物的其他三线态激发态性质，包括量子产率和寿命。所有结果表明，给定化合物通过T<>T形成成为潜在DNA光敏剂所需的阈值ET值在NFX和ANFX的三线态能量所定义的范围内（265 - 269 kJ/mol）。这为一个警示规则提供了依据：任何具有较高ET的化学物质（药物、化妆品、农药等）都必须考虑其潜在的光遗传毒性。
