Losartan and its interaction with copper(II): biological effects

Bioorg Med Chem. 2007 Oct 1;15(19):6418-24. doi: 10.1016/j.bmc.2007.06.056. Epub 2007 Jul 4.

Abstract

Losartan, the potassium salt of 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol, is an efficient antihypertensive drug. The vibrational FTIR and Raman spectra of Losartan (its anionic and protonated forms) are discussed. In addition, the copper(II) complex of Losartan was obtained and characterized as a microcrystalline powder. The metal center is bound to the ligand through the nitrogen atoms of the tetrazolate moiety as determined by vibrational spectroscopy. The compound is a dimer with the metal centers in a tetragonal distorted environment but the presence of a monomeric impurity has been determined by EPR spectroscopy. The antioxidant properties of the complex (superoxide dismutase mimetic activity) and its effect on the proliferation and morphology of two osteoblast-like cells in culture are reported. The new compound exerted more toxic effects on tumoral cells than the copper(II) ion and Losartan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Antioxidants / pharmacology
  • Binding, Competitive
  • Cations, Divalent
  • Cell Proliferation / drug effects*
  • Copper / chemistry
  • Copper / metabolism*
  • Disease Models, Animal
  • Electron Spin Resonance Spectroscopy
  • Ligands
  • Losartan / chemistry
  • Losartan / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Rats
  • Spectroscopy, Fourier Transform Infrared
  • Spectrum Analysis, Raman
  • Structure-Activity Relationship
  • Superoxide Dismutase / metabolism
  • Tetrazoles / chemistry
  • Tetrazoles / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antihypertensive Agents
  • Antioxidants
  • Cations, Divalent
  • Ligands
  • Tetrazoles
  • Copper
  • Superoxide Dismutase
  • Losartan