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

. 2017 Feb 15:127:174-186.

doi: 10.1016/j.ejmech.2016.12.045. Epub 2016 Dec 26.

Affiliations

• PMID: 28061347
• DOI: 10.1016/j.ejmech.2016.12.045

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

Ping Xu et al. Eur J Med Chem. 2017.

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 Aβ1-42 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 Aβ1-42 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.

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