Selective guanosine binding and cytotoxicity of a benzimidazole derived dinickel complex

J Inorg Biochem. 2007 Nov;101(11-12):1894-902. doi: 10.1016/j.jinorgbio.2007.04.006. Epub 2007 Apr 22.

Abstract

A water-soluble dinickel(II) complex of ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetrakis(2-benzimidazoyl) (EGTB) was synthesized and fully characterized. The complex crystallizes in a monoclinic system with space group P2(1)/c, a=10.125(1)A, b=28.393(3)A, c=11.026(1)A, and beta=98.966(2) degrees. The hexa-coordinated nickel(II) centers in the centrosymmetric complex adopt a distorted octahedron geometry. The complex binds to purine nucleotides covalently and shows a clear preference for guanosine-5'-monophosphate (5'-GMP) over adenosine-5'-monophosphate (5'-AMP). Its binding to calf thymus DNA (CT-DNA) induces a remarkable conformational variation. The cytotoxic activity of the complex was tested against diverse cell lines including human leukemic cell line U937, macrophage cell line Raw 264.7, human cervical cancer cell line Hela, and human hepatocytes cell line L02. The complex shows a significant inhibition against U937 and Raw 264.7 but little inhibition against Hela and L02.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / chemistry*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Circular Dichroism
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism*
  • Guanosine / chemistry*
  • Guanosine / metabolism
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Nickel / chemistry*
  • Nickel / metabolism
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology
  • U937 Cells

Substances

  • Benzimidazoles
  • Organometallic Compounds
  • Guanosine
  • Nickel
  • DNA
  • calf thymus DNA
  • benzimidazole