Synthesis, anticancer activities, interaction with DNA and mitochondria of manganese complexes

J Inorg Biochem. 2010 Nov;104(11):1141-7. doi: 10.1016/j.jinorgbio.2010.06.012. Epub 2010 Jul 12.

Abstract

Two new complexes [(Etdpa)MnCl(2)] and [(Adpa)Mn(Cl)(H(2)O)] (Etdpa = ethyl bis(2-pyridylmethyl)amino-2-propionate; Adpa = bis(2-pyridylmethyl)amino-2-propionic acid) were synthesized and characterized by spectral methods. The crystal structure of [(Etdpa)MnCl(2)] shows that the Mn(II) atom is coordinated by three N atoms (N1, N2, N3), one oxygen atom (O1) of the ligand (Etdpa) and two chloride atoms (Cl1, Cl2), forming a distorted octahedral geometry. The binding interaction between ct-DNA and the synthesized complexes was relatively weak, but they can inhibit the induced swelling of Ca(2+)-loaded mitochondria in a dose-dependent manner. The [(Adpa)Mn(Cl)(H(2)O)] can cause the obvious decrease of mitochondria membrane potential. The MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenpyltetra-zolium bromide) assay shows that the two Mn(II) complexes are more active against cancer cells. Especially [(Adpa)Mn(Cl)(H(2)O)] can inhibit the proliferation of glioma cells with IC(50) 9.5 μM. Experimental results indicate that the [(Adpa)Mn(Cl)(H(2)O)] could be a new potential antitumor complex to target the mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • DNA / chemistry
  • DNA / metabolism*
  • Drug Evaluation, Preclinical
  • Drug Interactions
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / pathology
  • Female
  • Formazans / metabolism
  • Glioma / drug therapy
  • Glioma / pathology
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Manganese / chemistry*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / metabolism*
  • Molecular Structure
  • Oxygen / chemistry
  • Rats
  • Reference Standards
  • Tetrazolium Salts / metabolism

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Formazans
  • Tetrazolium Salts
  • MTT formazan
  • Manganese
  • DNA
  • Oxygen