Interaction with biomacromolecules and antiproliferative activities of Mn(II), Ni(II), Zn(II) complexes of demethylcantharate and 2,2'-bipyridine

Spectrochim Acta A Mol Biomol Spectrosc. 2013 Jun:110:100-7. doi: 10.1016/j.saa.2013.03.015. Epub 2013 Mar 13.

Abstract

Three new transition metal complexes [Mn2(DCA)2(bipy)2]·5H2O (1), [M2(DCA)2(bipy)2(H2O)]·10H2O(M=Ni(II)(2);Zn(II)(3)), (DCA=demethylcantharate, 7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C8H8O5) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and X-ray diffraction techniques. Each metal ion was six-coordinated in complexes. Complex 1 has a Mn2O2 center. Complexes 2 and 3 have asymmetric binuclear structure. Great amount of intermolecular hydrogen-bonding and π-π(*) stacking interactions were formed in these complex structures. The DNA-binding properties of complexes were investigated by electronic absorption spectra and viscosity measurements. The DNA binding constants Kb/(Lmol(-1)) were 1.71×10(4) (1), 2.62×10(4) (2) and 1.59×10(4) (3) at 298 K. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) strongly through static quenching. The protein binding constants Ka/(L mol(-1)) were 7.27×10(4) (1), 4.55×10(4) (2) and 7.87×10(4) L mol(-1) (3) and binding site was one. The complexes bind more tightly with DNA and BSA than with ligands. Complexes 1 and 3 had stronger inhibition ratios than Na2(DCA) against human hepatoma cells (SMMC-7721) lines and human gastric cancer cells (MGC80-3) lines in vitro. Complex 3 showed the strongest antiproliferative activity against SMMC-7721 (IC50=29.46±2.12 μmol L(-1)) and MGC80-3 (IC50=27.02±2.38 μmol L(-1)), which shows potential in anti-cancer drug development.

MeSH terms

  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / metabolism
  • 2,2'-Dipyridyl / pharmacology*
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cantharidin / analogs & derivatives*
  • Cantharidin / chemistry
  • Cantharidin / metabolism
  • Cantharidin / pharmacology
  • Cattle
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • DNA / metabolism
  • Humans
  • Manganese / chemistry
  • Manganese / metabolism
  • Manganese / pharmacology*
  • Models, Molecular
  • Neoplasms / drug therapy
  • Nickel / chemistry
  • Nickel / metabolism
  • Nickel / pharmacology*
  • Serum Albumin, Bovine / metabolism
  • Zinc / chemistry
  • Zinc / metabolism
  • Zinc / pharmacology*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • demethylcantharidin
  • Serum Albumin, Bovine
  • Manganese
  • 2,2'-Dipyridyl
  • Nickel
  • DNA
  • Cantharidin
  • Zinc