New losartan-hydrocaffeic acid hybrids as antihypertensive-antioxidant dual drugs: Ester, amide and amine linkers

Eur J Med Chem. 2012 Apr:50:90-101. doi: 10.1016/j.ejmech.2012.01.043. Epub 2012 Jan 30.

Abstract

We report new examples of a series of losartan-hydrocaffeic hybrids that bear novel ester, amide and amine linkers. These compounds were made by linking hydrocaffeic acid to the side chain of losartan at the C-5 position of the imidazole ring through different strategies. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect and have increased antioxidant ability. Most of them reduced arterial pressure in rats better or as much as losartan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amides / metabolism
  • Amines / chemistry
  • Amines / metabolism
  • Angiotensin II / pharmacology
  • Animals
  • Antihypertensive Agents / chemical synthesis*
  • Antihypertensive Agents / pharmacology*
  • Antioxidants / chemical synthesis*
  • Antioxidants / pharmacology*
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / drug effects
  • Caffeic Acids / chemistry*
  • Caffeic Acids / pharmacology
  • Cells, Cultured
  • Esters / chemistry
  • Esters / metabolism
  • Hypertension / drug therapy
  • Losartan / chemistry*
  • Losartan / pharmacology
  • Male
  • Molecular Structure
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Vasoconstrictor Agents / pharmacology

Substances

  • Amides
  • Amines
  • Antihypertensive Agents
  • Antioxidants
  • Caffeic Acids
  • Esters
  • Vasoconstrictor Agents
  • Angiotensin II
  • Losartan