期刊文献+

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) 被引量:3

Alkynylplatinum(Ⅱ) 2,6-Bis(N-ethylbenzimidazol-2'-yl)pyridine Complexes:Effect of Alkynyl Ligand on G-quadruplex Binding Properties and Anticancer Activity
下载PDF
导出
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.
出处 《物理化学学报》 SCIE CAS CSCD 北大核心 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~~
关键词 G-四链体 铂(Ⅱ)配合物 抗癌活性 DNA作用 炔基配体 G-quadruplex Platinum(Ⅱ) complex Anticancer activity DNA interaction Alkynyl ligand
  • 相关文献

参考文献2

二级参考文献95

  • 1SUN Hongxia,XIANG Junfeng,ZHANG Yazhou,XU Guangzhi,XU Lianghua,TANG Yalin.Spectroscopic studies of the interaction between methyleneblue and G-quadruplex[J].Chinese Science Bulletin,2006,51(14):1687-1692. 被引量:2
  • 2Gellert M, Lipsett MN, Davies DR. Helix formation by guanylic acid. Proc Nat Acad Sci USA, 1962, 48(12): 2013-2018.
  • 3Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S. Quadruplex DNA: Sequence, topology and structure. Nucleic Acids Res, 2006, 34(19): 5402-5415.
  • 4Ambrus A, Chen D, Dai J, Bialis T, Jones RA, Yang D. Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution. Nucleic Acids Res, 2006, 34(9): 2723-2735.
  • 5Xu Y, Noguchi Y, Sugiyama H. The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution. Bioorg Med Chem, 2006, 14(16): 5584-5591.
  • 6Maizels N. Dynamic roles for G4 DNA in the biology of eukaryotic cells. Nat Struct Mol Biol, 2006, 13(12): 1055-1059.
  • 7Balasubramanian S, Neidle S. G-quadruplex nucleic acids as therapeutic targets. Curr Opin Chem Biol, 2009, 13(3): 345-353.
  • 8Riou JF. G-quadruplex interacting agents targeting the telomeric G-overhang are more than simple telomerase inhibitors. Curr Med Chem Anticancer Agents, 2004, 4(5): 439-443.
  • 9Matsugami A, Xu Y, Noguchi Y, Sugiyama H, Katahira M. Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions, as determined by NMR in a K+ solution. FEBS J, 2007, 274(14): 3545-3556.
  • 10Siddiqui-Jain A, Grand CL, Bearss DJ, Hurley LH. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-myc transcription. Proc Nat Acad Sci USA, 2002, 99(18): 11593-11598.

共引文献14

同被引文献12

引证文献3

二级引证文献4

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部