Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Aβ1-42 aggregation inhibitors and metal-chelating agents for Alzheimer's disease

Abstract

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 β-amyloid peptide (Aβ) aggregation inhibitor. The in vitro biological evaluation revealed that most of these newly synthesized compounds exhibited good inhibitory activity against self-induced Aβ_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 IC₅₀ values for Aβ_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.

Keywords: 3-hydroxypyridin-4-one; Antioxidant; Beta amyloid aggregation; Metal chelator; Resveratrol derivatives.