Differences in structure, physiological stability, electrochemistry, cytotoxicity, DNA and protein binding properties between two Ru(III) complexes

J Inorg Biochem. 2008 Feb;102(2):347-58. doi: 10.1016/j.jinorgbio.2007.09.008. Epub 2007 Oct 1.

Abstract

A novel Ru(III) complex, mer-[RuCl(3)(CH(3)CN)(dpq)] (1), has been synthesized and characterized by X-ray diffraction, where dpq=dipyrido[3,2-d:2',3'-f]quinoxaline. Its chemical and biological properties have been intensively compared with those of mer-[RuCl(3)(DMSO)(dpq)] (DMSO=dimethyl sulfoxide) (2). It has been found that the stability in buffered solutions and the reduction potential for the Ru(III)/Ru(II) couple can be modulated by changing the small molecule bonded to the Ru(III) center. Interactions of 1 with DNA have been investigated by DNA melting experiments, DNA competitive binding with EB (ethidium bromide), plasmid DNA cleavage experiments and viscosity measurements. The interaction of 1 and 2 with BSA (bovine serum albumin) has also been studied using fluorescent quenching method. The experimental results show that 1 exerts higher affinity towards DNA and BSA than 2 does. The cytotoxicity of 1 has been evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method, and 2 shows slightly higher anticancer potency than 1 does against all the cell lines screened. Attempts are made to clarify the possible antitumor mechanisms of these two complexes by analyzing the experimental results presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • DNA / metabolism*
  • Electrochemistry
  • Ethidium / metabolism
  • Humans
  • Molecular Structure
  • Organometallic Compounds* / chemical synthesis
  • Organometallic Compounds* / chemistry
  • Organometallic Compounds* / metabolism
  • Organometallic Compounds* / pharmacology
  • Protein Binding
  • Ruthenium* / chemistry
  • Ruthenium* / metabolism
  • Ruthenium* / pharmacology
  • Serum Albumin, Bovine / metabolism*

Substances

  • Organometallic Compounds
  • mer-trichloro(acrylonitrile)(dipyrido(3,2-d-2',3'-f)quinoxaline)ruthenium(III)
  • Serum Albumin, Bovine
  • Ruthenium
  • DNA
  • Ethidium