title: Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Aβ1-42aggregation 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 Aβ1-42aggregation, excellent antioxidant activity and potent metal chelating capability. Compounds 3i and 4f were identified as the most promising MTDLs with triple functions, possessing micromolar IC50values for Aβ1-42aggregation 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.
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 311402 Zhejiang, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 Zhejiang, PR China.
authors.forename: Minkui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 Zhejiang, PR China. Electronic address: shengr@zju.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Sheng
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 311402 Zhejiang, PR China. Electronic address: yongmin.ma@zcmu.edu.cn.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000975:Antioxidants / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002614:Chelating Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000378:metabolism; D000077543:Deferiprone; D015195:Drug Design; D007501:Iron / Q000378:metabolism; D062105:Molecular Docking Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects*; D017433:Protein Structure, Secondary; D011728:Pyridones / Q000737:chemistry*; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002614:Chelating Agents; D010446:Peptide Fragments; D066329:Protein Aggregates; D011728:Pyridones; D013267:Stilbenes; C075222:amyloid beta-protein (1-42); D000077543:Deferiprone; D003300:Copper; D007501:Iron; D000077185:Resveratrol
keywords: 3-hydroxypyridin-4-one; Antioxidant; Beta amyloid aggregation; Metal chelator; Resveratrol derivatives