PREPARATION, CHARACTERIZATION, AND ANTICANCER ACTIVITY OF A SERIES OF CIS-PTCL2 COMPLEXES LINKED TO ANTHRAQUINONE INTERCALATORS
PREPARATION, CHARACTERIZATION, AND ANTICANCER ACTIVITY OF A SERIES OF CIS-PTCL2 COMPLEXES LINKED TO ANTHRAQUINONE INTERCALATORS
复制标题
DOI：
10.1021/jm00105a063
复制
发表时间：
1991-01-01
影响因子：
7.3
通讯作者：
KATZHENDLER, J
中科院分区：
文献类型：
--
作者：
GIBSON, D;GEAN, KF;KATZHENDLER, J
合成了一系列新的顺式PtL2X2[L是单齿AQ-Y(CH2)(N)NH2，L2是双齿AQ-Y(CH2)(N)NH(CH2)2NH2；AQ=蒽醌，X=Cl，I，Y=NH，O]，其中的插层剂通过氨基烷基、氧烷基或聚乙二醇氨基连接链与顺式PtCl2单元相连，并在体外筛选出抗P388白血病的化合物。对选定的络合物进行了体内毒性研究。用元素分析、铂-195核磁共振波谱和傅立叶变换红外光谱对其结构进行了表征。1：1铂插层络合物的体外细胞毒活性明显高于1：2铂插层络合物。二氯化物络合物的活性始终高于它们的二碘化合物络合物。在1：1的铂插层络合物中，连接链较短的(n=2，3)具有最高的细胞毒活性。三种化合物，[[2-[[2-(anthraquinon-1-ylamino)ethyl]amine]ethyl]amine-N，N‘]二氯铂(II)、[[2-[[3-(anthraquinon-1-ylamino)propyl]amino]ethyl]amine-N，N’]二氯铂(II)和[[2-[[3-(anthraquinon-1-yloxy)propyl]amino]ethyl]amine-N，N‘]二氯铂(II)，在体外的活性与顺铂相当(ED50=2-4×10(-7)M)，而在摩尔基础上，其急性体内毒性明显低于顺铂。对P388白血病的体内筛选表明，这些化合物具有与顺铂相当的活性。
A new series of complexes of the type cis-PtL2X2 [where L is a monodentate AQ-Y(CH2)(n)NH2 and L2 is a bidentate AQ-Y(CH2)(n)NH(CH2)2NH2; AQ = anthraquinone, X = Cl, I, Y = NH, O] in which anthraquinone intercalators are tethered to the cis-PtCl2 unit via an (aminoalkyl)amino, (oxyalkyl)amino, or polyethylene glycol (aminoethyl)amino linker chains was prepared and screened in vitro against P388 leukemia. In vivo toxicity studies were carried out on selected complexes. All complexes were characterized by means of elemental analysis, Pt-195 NMR spectroscopy, and FTIR. The 1:1 Pt-intercalator complexes displayed much higher in vitro cytotoxic activities than the 1:2 Pt-intercalator complexes. The dichloride complexes were consistently more active than their diiodide counterparts. Among the 1:1 Pt-intercalator complexes those with the shorter linker chains (n = 2, 3) exhibited the highest cytotoxic activities. Three compounds, [[2-[[2-(anthraquinon-1-ylamino)ethyl]amine]ethyl]amine-N,N']dichloroplatinum(II), [[2-[[3-(anthraquinon-1-ylamino)propyl]amino]ethyl]amine-N,N']dichloroplatinum(II), and [[2-[[3-(anthraquinon-1-yloxy)propyl]amino]ethyl]amine-N,N']dichloroplatinum(II), were as active in vitro as cisplatin (ED50 = 2-4 x 10(-7) M) while on a molar basis their acute in vivo toxicity was significantly lower than that of cisplatin. In vivo screening against P388 leukemia indicated that these complexes have activity comparable to cisplatin.