Synthesis and Biological Activities of Hydroxytyrosol Ester Derivatives

A series of hydroxytyrosol (HT) derivatives were synthesized by modification of alcohol hydroxyl group of HT, twenty-five target compounds were obtained and characterized by NMR and HRMS. The antioxidant activities of those compounds were evaluated in three different assays. Except 3e and 3y, all other compounds demonstrated significant 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radical cation scavenging activity ranging from IC50 3.4 to 24.4 mu M, which were more potent than L-ascorbic acid (IC50 =24.8 mu M). Compounds 3b3d, 3f-3k, 3m-3x were better than Trolox (18.3 mu M). Moreover, the ferric reducing antioxidant power (FRAP) of all compounds were discovered to be more potent than L-ascorbic acid (40.7 mmol/g), except 3e, all other compounds (141.5-202.1 mmol/g) were better than Trolox (94.7 mmol/g). Compounds 3a-3d, 3f-3j, 3l-3m, 3o, 3q, 3t, 3v-3y exhibited more potent hydroxyl radical scavenging activity (IC50 =245.1-475.1 mu M) than L-ascorbic acid (554.4 mu M) and Trolox (500.4 mu M). Compounds 3q, 3t and 3y exhibited more potent u-Glucosidase inhibition activity (39.1-52.4 mu M) than Acarbose (60.9 mu M). Compounds 3a, 3d, 3f-3m, 3s-3t, 3v-3y showed some acetylcholinesterase inhibition activities, compounds 3a, 3d, 3f-3j, 31-3m, 3o-3p, 3s-3t, 3w showed some butyrylcholinesterase inhibition activities.