Acta Phys. -Chim. Sin. ›› 2015, Vol. 31 ›› Issue (12): 2386-2394.doi: 10.3866/PKU.WHXB201510137

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

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

Zhi-Ze. OU*(),Bao-Long. JU,Yun-Yan. GAO*(),Zi-Chao. WANG,Gan. HUANG,Yi-Meng. QIAN   

  • Received:2015-07-20 Published:2015-12-04
  • Contact: Zhi-Ze. OU,Yun-Yan. GAO;
  • Supported by:
    the National Natural Science Foundation of China(21073143);“Chunhui Project” from the Ministry of Education ofChina(Z2009-1-71002, Z2009-1-71006);Graduate Starting Seed Fund of Northwestern Polytechnical University (NPU), China(Z2015152);NPU Foundation for Graduate Innovation, China


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 cmyc 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 (ΔTm) of more than 24 ℃, but complex 4, containing a propyne moiety, only induces ΔTm 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.

Key words: G-quadruplex, Platinum(Ⅱ) complex, Anticancer activity, DNA interaction, Alkynyl ligand