Drobník J
Cancer Chemother Pharmacol. 1983;10(3):145-9. doi: 10.1007/BF00255749.
Contemporary ideas about the mechanism of antitumor activity of platinum complexes are reviewed and discussed. The induction of SOS functions in bacteria is emphasized and an analogous mechanism in animal cells is suggested. The fate of the leaving ligand in the body is not known. Therefore the complex which reaches the target DNA may be very different from the applied compound. Even the amino ligand may be detached in the body, probably as part of the detoxication by binding to proteins. In the case of fast or medium-speed reactive complexes most of the platinum is inactivated by binding to proteins, whereas slow-reacting drugs are mostly excreted unchanged in the urine. Thus, the quantity of the complex which reaches the target is also difficult to assess. Due to peculiar pharmacokinetics, the results obtained with poorly soluble compounds administered in the solid form cannot be compared with those obtained in true solutions. There are many reasons for believing that the study of a coordination anticancer drug may contribute to our understanding of cancer growth and its reversal.
本文综述并讨论了关于铂配合物抗肿瘤活性机制的当代观点。着重强调了细菌中SOS功能的诱导,并提出了动物细胞中的类似机制。体内离去配体的命运尚不清楚。因此,到达靶DNA的配合物可能与所施用的化合物有很大不同。甚至氨基配体在体内也可能被分离,可能是作为与蛋白质结合进行解毒的一部分。对于快速或中等反应性的配合物,大部分铂通过与蛋白质结合而失活,而反应缓慢的药物大多以原形经尿液排出。因此,到达靶标的配合物数量也难以评估。由于特殊的药代动力学,以固体形式施用的难溶性化合物所获得的结果无法与在真实溶液中获得的结果进行比较。有许多理由相信,对配位抗癌药物的研究可能有助于我们理解癌症的生长及其逆转。