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Polypyridyl Complexes of Ruthenium(II): Stabilization of G-quadruplex DNA and Inhibition of Telomerase Activity

  1. Dr. Du Liu1,†,
  2. Yanan Liu1,†,
  3. Chuan Wang1,
  4. Prof. Shuo Shi3,
  5. Dongdong Sun1,
  6. Dr. Feng Gao2,*,
  7. Prof. Qianling Zhang4,*,
  8. Prof. Jie Liu1,*

Article first published online: 21 MAY 2012

DOI: 10.1002/cplu.201200039

Issue

ChemPlusChem

ChemPlusChem

Volume 77, Issue 7, pages 551–562, July 2012

Additional Information

How to Cite

Liu, D., Liu, Y., Wang, C., Shi, S., Sun, D., Gao, F., Zhang, Q. and Liu, J. (2012), Polypyridyl Complexes of Ruthenium(II): Stabilization of G-quadruplex DNA and Inhibition of Telomerase Activity. ChemPlusChem, 77: 551–562. doi: 10.1002/cplu.201200039

Author Information

  1. 1

    Department of Chemistry, Jinan University, Guangzhou 510632 (P. R. China), Fax: (+86) 20-8522-1263

  2. 2

    School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China)

  3. 3

    Department of Chemistry, Tongji University, Shanghai 200092 (P. R. China)

  4. 4

    Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518061 (P. R. China)

  1. †

    These authors contributed equally to this work.

*School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China)

  1. †

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 5 JUL 2012
  2. Article first published online: 21 MAY 2012
  3. Manuscript Revised: 17 APR 2012
  4. Manuscript Received: 29 FEB 2012

Funded by

  • National Natural Science Foundation of China. Grant Number: 20871056, 21171070
  • Planned Item of Science and Technology of Guangdong Province. Grant Number: c1011220800060
  • Fundamental Research Funds for the Central Universities
  • Planned Item of Science
  • Fundamental Research Foundation of Shenzhen City. Grant Number: JC201005250058A

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Keywords:

  • antitumor agents;
  • bioinorganic chemistry;
  • DNA;
  • G-quadruplex DNA;
  • ruthenium complexes;
  • telomerase

Abstract

Two ruthenium(II) complexes [Ru(phen)2(tip)](ClO4)2 (1) and [Ru(bpy)2(tip)](ClO4)2 (2; phen=1,10-phenanthroline, bpy=2,2’-bipyridine, tip=2-thiophenimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, 1H NMR spectroscopy, and electrospray ionization-mass spectrometry to explore the role of metal complexes as novel telomeric quadruplex stabilizers. The different quadruplex binding properties of these compounds were evaluated by absorption and emission analyses, circular dichroism spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, NMR spectroscopy, and molecular modeling. The results show that both complexes can well induce and stabilize different G-quadruplex structures using a 1:1 [quadruplex]/[complex] binding mode ratio. Complex 1 exhibits higher interaction ability at 1.43×106 M−1 binding affinity and superior G-quadruplex selectivity over duplex DNA through multiple interaction (mainly intercalating) with the G-quadruplex at the 3’-terminal face. Furthermore, polymerase chain reaction (PCR)-stop assay, electrophoretic mobility shift assay, telomerase repeat amplification protocol, and MTT assay demonstrate that complex 1 not only can stabilize dimer forms of the G-quadruplex at low concentrations but also exhibit better inhibitory activity for telomerase and cancer cells. The results suggest that complex 1 may be a potential telomerase inhibitor for cancer chemotherapy.

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