Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum complexes: Comparison of effects of geometry and polyfunctionality on biological activity

作     者：Qu, Y Rauter, H Fontes, APS Bandarage, R Kelland, LR Farrell, N 

作者机构：Virginia Commonwealth Univ Dept Chem Richmond VA 23284 USA Inst Canc Res CRC Ctr Canc Therapeut Sutton SM2 5NG Surrey England 

出 版 物：《JOURNAL OF MEDICINAL CHEMISTRY》 (医药化学杂志)

年 卷 期：2000年第43卷第16期

页      面：3189-3192页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：NCI NIH HHS [R01-CA78754] Funding Source: Medline 

主　　题：胺类/化学 抗肿瘤药/化学合成 抗肿瘤药/化学 抗肿瘤药/药理学 DNA 肿瘤/代谢 抗药性 肿瘤 药物筛选试验 抗肿瘤 有机金属化合物/化学合成 有机金属化合物/化学 有机金属化合物/药理学 铂 构效关系 肿瘤细胞 培养的 人类 

摘      要：The synthesis of two new isomeric trifunctional dinuclear platinum complexes of formula [{PtCl(NH3)(2)}mu-NH2(CH2)(6)NH2-{PtCl2(NH3)}](+) (1,2/c,c and 1,2/t,c) is reported. Their biological activity in selected human tumor cell lines sensitive and resistant to CDDP (cisplatin, cis-[Pt(NH3)(2)Cl-2]) is described and compared with the profile for their bifunctional analogues, [{cis/trans-PtCl(NH3)(2)}(2)mu-NH2(CH2)(6)NH2](2+). The trifunctional dinuclear platinum complexes showed a unique profile of cytotoxicity against human cancer cell lines, with low resistance factors in A2780, CH1, and 41M cell. lines. The resistance factor is dependent on the geometry of the Pt coordination spheres - suggesting that these may be associated with DNA-binding modes. Retention of activity against CDDP-resistant cell lines and a different spectrum of activity compared to CDDP and also within different classes of polynuclear platinum complexes suggest that not only are they mechanistically different from mononuclear platinum complexes but also each individual class of polynuclear platinum structure may have its own unique character.