Trans-Platinum Complexes in Cancer Therapy

被引:166
作者
Coluccia, Mauro [2 ]
Natile, Giovanni [1 ]
机构
[1] Univ Bari, Dept Farmacochim, I-70125 Bari, Italy
[2] Univ Bari, Dept Sci Biomed & Oncol Umana, I-70124 Bari, Italy
关键词
Platinum antitumor drugs; trans configuration; DNA interaction; cell cycle perturbation; gene expression profiling;
D O I
10.2174/187152007779314080
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The research of new platinum drugs active towards cisplatin refractory/resistant tumors has been mostly focussed on compounds with cis geometry because transplatin, the trans-isomer of cisplatin, is inactive. It is widely accepted that transplatin inactivity stems from two major factors: i) the kinetic instability promoting its deactivation and ii) the formation of DNA adducts characterized by a regioselectivity and a stereochemistry different from those of cisplatin. However, several exceptions to the general rule that the presence of two leaving groups in cis positions is necessary for antitumor activity of platinum complexes, have been reported. Substitution of transplatin ammine ligands by aromatic N-donor heterocycles, branched aliphatic amines, or imino ligands has lead to compounds with relevant in vitro tumor cell growth inhibitory potency, often active towards cisplatin refractory/resistant tumor cells, and in some cases endowed with significant activity also in vivo. From a mechanistic point of view, substitution of bulky ligands for ammines can retard substitution of the two chloride ligands, thus reducing the kinetic instability of the trans-platinum compounds. On the other hand, the formation of DNA adducts qualitatively and quantitatively different from those of cisplatin strongly supports the hypothesis that antitumor-active trans-platinum complexes can have a different spectrum of activity. It is hoped that the increasing knowledge of the biochemical and cellular processes underlying the antitumor-activity of trans-platinum complexes will foster their clinical development.
引用
收藏
页码:111 / 123
页数:13
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