CYTOTOXICITY AND ANTITUMOR-ACTIVITY OF BIS(PLATINUM) COMPLEXES - A NOVEL CLASS OF PLATINUM COMPLEXES ACTIVE IN CELL-LINES RESISTANT TO BOTH CISPLATIN AND 1,2-DIAMINOCYCLOHEXANE COMPLEXES
CYTOTOXICITY AND ANTITUMOR-ACTIVITY OF BIS(PLATINUM) COMPLEXES - A NOVEL CLASS OF PLATINUM COMPLEXES ACTIVE IN CELL-LINES RESISTANT TO BOTH CISPLATIN AND 1,2-DIAMINOCYCLOHEXANE COMPLEXES
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DOI：
10.1021/jm00170a021
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发表时间：
1990-08-01
影响因子：
7.3
通讯作者：
HACKER, MP
中科院分区：
文献类型：
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作者：
FARRELL, N;QU, Y;HACKER, MP
报告了通式 [{PtX2- (L)}2H2N(CH2)nNH2]（L = NH3，X = Cl 或 X2 = malonato 或其中 L = py，X = Cl）的双（铂）复合物的体外细胞毒性和体内抗肿瘤活性。氯化物络合物 [{PtCl2(NH3)}2H2N(CH2)nNH2] 可能以三种可能的异构体形式存在：含有两个顺式构型配位单元 (2,2/c,c) 和两个反式构型配位单元 (2,2/t,t) 和混合顺式、反式异构体 (2,2/c,t) 的异构体，其合成在此报告。举例说明了具有位阻二胺主链例如2,5-二甲基-2,5-己二胺的其他络合物的制备。比较所有复合物的生物活性。 2,2/c,c 复合物在组织培养中对顺铂及其 1,2-二氨基环己烷 (dach) 类似物具有抗性的细胞中特别活跃。 2,2/c,c复合物对L1210/0细胞中DNA合成的抑制作用与顺铂相当。至少一个顺式-[Pt(胺)2]单元的存在似乎对于顺铂敏感的细胞系中的活性是必要的。
The in vitro cytotoxicity and in vivo antitumor activity of bis(platinum) complexes of general formula [{PtX2- (L)}2H2N(CH2)nNH2] (L = NH3, X = Cl or X2 = malonato or where L = py, X = Cl) is reported. Chloride complexes [{PtCl2(NH3)}2H2N(CH2)nNH2] may exist as three possible isomers: those containing both coordination units in the cis configuration (2,2/c,c) both coordination units in the trans configuration (2,2/t,t) and the mixed cis,trans species (2,2/c,t), whose synthesis is reported here. The preparation of further complexes with sterically hindered diamine backbones, such as 2,5-dimethyl-2,5-hexanediamine, is exemplified. The biological activity of all complexes were compared. The 2,2/c,c complexes are particularly active in tissue culture in cells resistant both to cisplatin and its 1,2-diaminocyclohexane (dach) analogue. The inhibition of DNA synthesis in L1210/0 cells by the 2,2/c,c complexes is equivalent to that of cisplatin. The presence of at least one cis-[Pt(amine)2] unit appears necessary for activity in cell lines sensitive to cisplatin.