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

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.

Graphical abstractTwo are better than one: Hypertension and oxidative stress are two factors that come together in cardiovascular damage in hypertensive patients. New hybrid drugs that link antihypertensive and antioxidant molecules through ester, amide and amine groups maintain both antihypertensive and antioxidant effects and may be more useful than just an antihypertensive for controlling hypertension and preventing hypertension-induced cardiovascular damage.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Losartan and hydrocaffeic acid were linked through ester, amide and amine linkers. ► The prepared new hybrids showed a dual antihypertensive-antioxidant effect. ► Antioxidant ability of these hybrids was 3–9 times that of losartan. ► Hybrids inhibited contraction of cultured smooth muscle cells as good as losartan. ► Most of the hybrids reduced arterial pressure in rats better or as much as losartan.