炔基配体对2,6-双(N-乙基苯并咪唑)吡啶炔基铂(Ⅱ)配合物与G-四链体作用及抗癌活性的影响(英文)  

Alkynylplatinum(Ⅱ) 2,6-Bis(N-ethylbenzimidazol-2'-yl)pyridine Complexes:Effect of Alkynyl Ligand on G-quadruplex Binding Properties and Anticancer Activity

作　　者：欧植泽[1] 句宝龙 高云燕[1] 王子超[1] 黄干[1] 钱一梦 

机构地区：[1]西北工业大学理学院,空间应用物理与化学教育部重点实验室,西安710072

出　　处：《物理化学学报》2015年第12期2386-2394,共9页Acta Physico-Chimica Sinica

基　　金：supported by the National Natural Science Foundation of China(21073143);“Chunhui Project”from the Ministry of Education of China(Z2009-1-71002,Z2009-1-71006);Graduate Starting Seed Fund of Northwestern Polytechnical University(NPU),China(Z2015152);NPU Foundation for Graduate Innovation;China~~

摘　　要：合成了三种2,6-双(N-乙基苯并咪唑)吡啶炔基铂(Ⅱ)配合物(2-4),其中配合物2的炔基配体为抗癌药物埃罗替尼.利用紫外-可见(UV-Vis)吸收光谱,圆二色(CD)光谱,荧光共振能量转移(FRET)等方法研究了铂(Ⅱ)配合物与人体端粒(Hetelo)和c-myc原癌基因(c-myc)G-四链体的相互作用.实验结果表明,所合成的铂配合物与G-四链体具有较强的相互作用(K_a>10~6L·mol^(-1)),在无碱金属离子存在条件下能诱导G-四链体的形成.含苯乙炔基团的配合物2、3能使c-myc G-四链体的熔解温度上升24℃以上,而含丙炔基团的铂配合物4仅使c-myc G-四链体的熔解温度升高9.0℃,表明炔基结构对铂(Ⅱ)配合物与G-四连体的作用有较大影响.配合物2对人肺癌细胞A549的细胞毒性明显高于埃罗替尼及其他两种配合物3、4.Three alkynylplatinum（Ⅱ）-2,6-bis（N-ethylbenzimidazol-2＇-yl）pyridine complexes 2-4 were synthesized and characterized. The alkynyl ligand in complex 2 is the anticancer drug erlotinib. The interactions between the Pt（Ⅱ） complexes and G-quadruplexes, including human telomeric （Hetelo） and c- myc oncogene （c-myc） quadruplexes, were investigated using UV-Vis spectroscopy, circular dichroism （CD）, and fluorescence resonance energy transfer （FRET） melting assays. These studies show that the Pt（Ⅱ） complexes 2-4 have high affinities for G-quadruplexes （Ka 〉 106 L. mol-1）, and can promote the formation of G-quadruplexes even in the absence of alkali cations. The Pt（Ⅱ） complexes 2 and 3, containing a phenylacetylene moiety, induce a high degree of stabilization of the c-myc G-quadruplex, with a melting temperature increase （ATm） of more than 24 ℃, but complex 4, containing a propyne moiety, only induces ATm of 9.0 ℃. These results indicate that the structure of the alkynyl ligand is important in the interactions between Pt（Ⅱ） complexes and G-quadruplexes. The cytotoxicity of complex 2 to the human adenocarcinoma A549 cell line is higher than those of complexes 3, 4, and erlotinib.

关 键 词：G-四链体 铂(Ⅱ)配合物 抗癌活性 DNA作用 炔基配体 

分 类 号：O641.4[理学—物理化学]