Losartan-antioxidant hybrids: novel molecules for the prevention of hypertension-induced cardiovascular damage.
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.
Departamento de Quimica Organica, Universidad de Alcalá, Campus Universitario, 28871-Alcalá de Henares, Madrid, Spain.
Gonzalo
G
García
Manuel
M
Rodríguez-Puyol
Ramón
R
Alajarín
Isabel
I
Serrano
Patricia
P
Sánchez-Alonso
Mercedes
M
Griera
Juan J
JJ
Vaquero
Diego
D
Rodríguez-Puyol
Julio
J
Alvarez-Builla
María L
ML
Díez-Marqués
D000438:Alcohols / Q000737:chemistry; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000097:blood; D004952:Esters / Q000737:chemistry; D005353:Fibronectins / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D019808:Losartan / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000438:Alcohols; D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D024042:Collagen Type I; D004952:Esters; D005353:Fibronectins; D000804:Angiotensin II; D019808:Losartan