Losartan-antioxidant hybrids: novel molecules for the prevention of hypertension-induced cardiovascular damage

J Med Chem. 2009 Nov 26;52(22):7220-7. doi: 10.1021/jm9003957.

Abstract

We report the first examples of a new series of antioxidant-sartan hybrids (AO-sartans), which were made by adding an antioxidant fragment to the hydroxymethyl side chain of losartan. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect with increased antioxidant ability. In hypertensive rats, these compounds show properties that suggest they may be more useful than losartan for controlling hypertension and preventing hypertension-induced cardiovascular damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II Type 1 Receptor Blockers / blood
  • Angiotensin II Type 1 Receptor Blockers / chemistry
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Antioxidants / chemistry*
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / prevention & control*
  • Cells, Cultured
  • Collagen Type I / blood
  • Esters / chemistry
  • Fibronectins / blood
  • Humans
  • Hypertension / blood
  • Hypertension / complications*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Losartan / blood
  • Losartan / chemistry*
  • Losartan / pharmacology*
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Alcohols
  • Angiotensin II Type 1 Receptor Blockers
  • Antioxidants
  • Collagen Type I
  • Esters
  • Fibronectins
  • Angiotensin II
  • Losartan