Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR8601, Université Paris Descartes, 45 Rue des Saints-Pères, 75006, Paris, France.
J Biol Inorg Chem. 2010 Aug;15(6):841-50. doi: 10.1007/s00775-010-0648-8. Epub 2010 Mar 24.
Enantiomeric complexes of formula [PtCl(2)L(2)] [L(2) is (R)-(+)-BINAP and (S)-(-)-BINAP, where BINAP is 2,2'-bis(diphenylphosphane)-1,1'-binaphthyl, and (R)-(+)-DABN and (S)-(-)-DABN, where DABN is 1,1'-binaphthyl-2,2'-diamine], were tested for their cytotoxic activity against three cancer cell lines and for their ability to bind to the human telomeric sequence folded in the G-quadruplex structure. Similar experiments were carried out on prototypal complexes cisplatin and cis-[PtCl(2)(PPh(3))(2)] for comparison. Platinum complexes containing phosphanes proved less cytotoxic to cancer cell lines and less likely to interact with the nucleobases of the G-quadruplex than those containing amines; in both cases the S-(-) isomer was more active than the R-(+) counterpart. More specifically, whereas all the platinum complexes were able to platinate the G-quadruplex structure from the human telomeric repeat, the extent and sites of platination depended on the nature of the ligands. Complexes containing (bulky) phosphanes interacted only with the adenines of the loops, whereas those containing the less sterically demanding amines interacted with adenines and some guanines of the G-quartet.
[PtCl(2)L(2)]的对映体配合物[L(2)为(R)-(+)-BINAP 和 (S)-(-)-BINAP，其中 BINAP 为 2,2'-双(二苯基膦基)-1,1'-联萘，以及 (R)-(+)-DABN 和 (S)-(-)-DABN，其中 DABN 为 1,1'-联萘-2,2'-二胺]，其对三种癌细胞系的细胞毒性活性以及与折叠在 G-四链体结构中的人端粒序列结合的能力进行了测试。为了进行比较，对原型配合物顺铂和 cis-[PtCl(2)(PPh(3))(2)]进行了类似的实验。含膦的铂配合物对癌细胞系的细胞毒性较低，与 G-四链体的碱基相互作用的可能性也较低；在这两种情况下，S-(-)异构体比 R-(+)异构体更活跃。更具体地说，虽然所有的铂配合物都能够使来自人端粒重复的 G-四链体结构铂化，但铂化的程度和部位取决于配体的性质。含（大体积）膦的配合物仅与环上的腺嘌呤相互作用，而那些含要求不那么苛刻的胺的配合物与腺嘌呤和 G-四聚体的一些鸟嘌呤相互作用。
