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.
García
Gonzalo
G
Departamento de Quimica Organica, Universidad de Alcalá, Campus Universitario, 28871-Alcalá de Henares, Madrid, Spain.
Rodríguez-Puyol
Manuel
M
Alajarín
Ramón
R
Serrano
Isabel
I
Sánchez-Alonso
Patricia
P
Griera
Mercedes
M
Vaquero
Juan J
JJ
Rodríguez-Puyol
Diego
D
Alvarez-Builla
Julio
J
Díez-Marqués
María L
ML
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