JBIC Journal of Biological Inorganic Chemistry

, Volume 17, Issue 1, pp 81–96

Chiral ruthenium(II) anthraquinone complexes as dual inhibitors of topoisomerases I and II

  • Jun-Feng Kou
  • Chen Qian
  • Jin-Quan Wang
  • Xiang Chen
  • Li-Li Wang
  • Hui Chao
  • Liang-Nian Ji
Original Paper

DOI: 10.1007/s00775-011-0831-6

Cite this article as:
Kou, JF., Qian, C., Wang, JQ. et al. J Biol Inorg Chem (2012) 17: 81. doi:10.1007/s00775-011-0831-6

Abstract

DNA topoisomerases (I and II) have been one of the excellent targets in anticancer drug development. Here two chiral ruthenium(II) anthraquinone complexes, Δ- and Λ-[Ru(bpy)2(ipad)]2+, where bpy is 2,2′-bipyridine and ipad is 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline, were synthesized and characterized. As expected, both of the Ru(II) complexes intercalate into DNA base pairs and possess an obviously greater affinity with DNA. Topoisomerase inhibition and DNA strand passage assay confirmed that the two complexes are efficient dual inhibitors of topoisomerases I and II by interference with the DNA religation. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against HeLa, MCF-7, HepG2 and BEL-7402 tumor cell lines. Flow cytometry analysis shows an increase in the percentage of cells with apoptotic morphological features in the sub-G1 phase for Ru(II) complexes. Nuclear chromatin cleavage has also been observed from AO/EB staining assay and alkaline single-cell gel electrophoresis (comet assay). The results demonstrated that Δ- and Λ-[Ru(bpy)2(ipad)]2+ act as dual inhibitors of topoisomerases I and II, and cause DNA damage that can lead to cell cycle arrest and/or cell death by apoptosis.

Graphical abstract

Chiral ruthenium(II) anthraquinone complexes Δ- and Λ-[Ru(bpy)2(ipad)]2+ are demonstrated to be efficient dual inhibitors of topoisomerases I and II, and cause DNA damage that can lead to cell cycle arrest and/or cell death by apoptosis.

Keywords

Ruthenium(II) complexes DNA binding Topoisomerase inhibition Cytotoxicity Apoptosis 

Copyright information

© SBIC 2011

Authors and Affiliations

  • Jun-Feng Kou
    • 1
  • Chen Qian
    • 1
  • Jin-Quan Wang
    • 1
    • 3
  • Xiang Chen
    • 1
  • Li-Li Wang
    • 1
  • Hui Chao
    • 1
    • 2
  • Liang-Nian Ji
    • 1
  1. 1.MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical EngineeringSun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  2. 2.State Key Laboratory of Coordination ChemistryNanjing UniversityNanjingPeople’s Republic of China
  3. 3.Guangdong Pharmaceutical UniversityGuangzhouPeople’s Republic of China

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