Synthesis, characterisation, activities, cell uptake and DNA binding of [{trans-PtCl(NH3)2} {μ-(H2N(CH2)6NH2)} trans-PdCl(NH3)2](NO3)Cl
Synthesis, characterisation, activities, cell uptake and DNA binding of [{trans-PtCl(NH3)2} {μ-(H2N(CH2)6NH2)} trans-PdCl(NH3)2](NO3)Cl
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DOI：
10.1016/j.ejmech.2004.07.012
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发表时间：
2004-11-01
影响因子：
6.7
通讯作者：
Zhang, M
中科院分区：
文献类型：
--
作者：
Huq, F;Daghriri, H;Zhang, M
双核复合物：[[trans-PtCI(NH3)(2)} (mu-(H2N(CH2)(6)NH2)) (trans-PdCl(NH3)(2)](NO3)Cl（代号 DHD）已合成并表征。针对人类癌细胞系（包括卵巢癌：A2780、A2780(cisR)）的活性、细胞摄取、与 DNA 以及该化合物与 pBR322 质粒和鲑鱼精子 DNA 相互作用的性质已经确定。该化合物被发现对卵巢癌细胞系 A2780、A2780(cisR) 和 A2780(ZD0473R) 表现出显着的抗癌活性——大约是顺铂对 A2780 细胞系的活性的两倍，大约是顺铂对 A2780 细胞系的活性的五倍。 A2780(cisR) 和 A2780(ZD0473R) 细胞系。 DHD 的较高活性表明该化合物能够克服 A2780(cisR) 和 A2780(ZD0473R) 细胞系中的多种耐药机制。 DHD 被认为与双链 DNA 形成一系列链间 GG 加合物，从而诱导 DNA 的整体变化 与顺铂和 ZD0473 不同，顺铂和 ZD0473 主要形成链内加合物，诱导 DNA 链局部扭结。随着 DHD 浓度的增加，BamH1 对 I 型和 II 型 pBR322 质粒 DNA 的消化作用增强，这支持了 DHD 与 pBR322 质粒 DNA 的链间结合导致 DNA 整体变化的观点。 构象。 (C) 2004 年爱思唯尔 SAS。保留所有权利。
The dinuclear complex: [[trans-PtCI(NH3)(2)} (mu-(H2N(CH2)(6)NH2)) (trans-PdCl(NH3)(2)](NO3)Cl (code named DHD) has been synthesized and characterized. The activity against human cancer cell lines including ovarian: A2780, A2780(cisR), cell up take, level of binding with DNA and nature of interaction of the compound with pBR322 plasmid and salmon sperm DNAs have been determined. The compound is found to exhibit significant anticancer activity against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R)--about two times as active as cisplatin against A2780 cell line, about five times as active as cisplatin against A2780(cisR) and A2780(ZD0473R) cell lines. The higher activity of DHD suggests that the compound is able to overcome multiple mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R) cell lines. DHD is believed to form a range of interstrand GG adducts with duplex DNA that induces global changes in the DNA conformation, unlike cisplatin and ZD0473 that form mainly intrastrand adducts that induces a local kink id a DNA strand. Increasing prevention of BamH1 digestion of form I and form II pBR322 plasmid DNA with the increase in concentration of DHD provides support to the idea that the interstrand binding of DHD with pBR322 plasmid DNA brings about global changes in DNA conformation. (C) 2004 Elsevier SAS. All rights reserved.