Structure/antioxidant activity relationship of hydroxytyrosol analogues and their fatty acid esters

Hydroxytyrosol 1 (R=H) is a natural polyphenolic antioxidant that protects cells against oxidative stress.1 It also reduces risks connected with aging pathogenesis,2 cancer proliferation3 and HIV infection.4 In spite of these remarkable properties, its amphiphilic character makes difficult its solubilization in lipid environment and hampers its use as nutraceutical or antioxidant additive. Hydroxytyrosyl esters (1, R= CO(CH2)nCH3) overcome these limitations.5, 6 In order to test the effect on the antioxidant activity of both the alcohol chain lenght and the position of the catechol function, we have developed the synthesis of the hydroxytyrosol analogues 2 and 3 (R= H) and their esters of fatty acids (R= CO(CH2)nCH3, n=0-16) using a recently published procedure based on a chemo and regioselective aromatic hydroxylation of the corresponding phenol derivatives by using 2-iodoxybenzoic acid (IBX).5 The antioxidant activity of all compounds was evaluated by both chemical (ABTS assay) and biological (DCF assay) experiments in order to establish possible structure/antioxidant activity relationship. Experiments have evidenced interesting correlation between in vitro antioxidant capacity and chemical structure, while in cell environment the antioxidant activity follows the peculiar trend already established with hydroxytyrosyl esters.6