Baguley Bruce C, Wakelin Laurence P G, Jacintho Jason D, Kovacic Peter
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1000, New Zealand.
Curr Med Chem. 2003 Dec;10(24):2643-9. doi: 10.2174/0929867033456332.
Reactive oxygen species (ROS) are produced continuously in living cells as a by-product of respiration and other metabolic activity. Some ROS may react with DNA, and in some cases may abstract an electron from the double helix, leading to long range electron transfer (ET) reactions. Thus, the DNA of living cells may be in a continuous state of ET. We consider here whether acridine-based anticancer or antimicrobial drugs, which bind to DNA by intercalation, might either donate electrons to, or accept electrons from, the double helix, thus actively participating in ET reactions. We focus in particular on two acridine-based drugs that have been tested against human cancer in the clinic. Amsacrine is a 9-anilinoacridine derivative that appears to act as an electron donor in ET reactions on DNA, while N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) may act as an electron acceptor. Such reactions may make important contributions to the antitumor activity of these drugs.
活性氧（ROS）作为呼吸作用和其他代谢活动的副产物，在活细胞中持续产生。一些ROS可能与DNA发生反应，在某些情况下可能从双螺旋结构中夺取一个电子，从而引发长程电子转移（ET）反应。因此，活细胞的DNA可能处于持续的电子转移状态。我们在此探讨通过嵌入作用与DNA结合的吖啶类抗癌或抗菌药物是否可能向双螺旋结构供电子或从双螺旋结构接受电子，从而积极参与电子转移反应。我们特别关注两种已在临床中针对人类癌症进行测试的吖啶类药物。安吖啶是一种9-苯胺基吖啶衍生物，在DNA上的电子转移反应中似乎充当电子供体，而N-[2-(二甲基氨基)乙基]吖啶-4-甲酰胺（DACA）可能充当电子受体。此类反应可能对这些药物的抗肿瘤活性做出重要贡献。
