Hydroxytyrosol analogues and their fatty acid esters. Synthesis and structure/antioxidant activity relationships

Hydroxytyrosol 1 (R=H) is a natural polyphenolic antioxidant present in leafs and fruits of olive tree. Hydroxytyrosol protects cells against oxidative stress, reduces risks connected with aging pathogenesis, cancer proliferation and HIV infection. However, its hydrophilicity has hampered its use as nutraceutical or antioxidant additive in oils or fats. Hydroxytyrosyl esters (1, R= CO(CH2)nCH3) overcame these limitations. , In order to test the effect on the antioxidant activity of structural modifications of 1, 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) extending a recently published procedure.5 To establish possible relationships between structural changes and antioxidant activity, all compounds were analyzed by both chemical (ABTS assay) and biological (DCF assay) antioxidant experiments. In vitro studies evidenced interesting enhancement of TEAC in derivatives containing either longer alcoholic chain, modification of catechols position (1,2-dihydroxyphenyl) or both. In cell environment, the antioxidant activity is less influenced by structural modifications and follows the peculiar trend (cut-off effect) already established with hydroxytyrosyl esters.6