Xu_2017_Eur.J.Med.Chem_127_174

A series of deferiprone-resveratrol hybrids have been designed and synthesized as multitarget-directed ligands (MTDLs) through merging the chelating moiety 3-hydroxypyridin-4-one into the structure of resveratrol, a natural antioxidant agent and beta-amyloid peptide (Abeta) aggregation inhibitor. The in vitro biological evaluation revealed that most of these newly synthesized compounds exhibited good inhibitory activity against self-induced Abeta(1-42) aggregation, excellent antioxidant activity and potent metal chelating capability. Compounds 3i and 4f were identified as the most promising MTDLs with triple functions, possessing micromolar IC(50) values for Abeta(1-42) aggregation inhibition, greater 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(*+)) scavenging activity than Trolox and similar pFe(III) values to that of deferiprone.