title: Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease.
abstract: A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Aβ) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Aβ self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD.
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; Zhejiang Pharmaceutical College, Ningbo 315000, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Digiacomo
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Tu
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Chu
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
authors.forename: Qiuhe
authors.initials: Q
authors.lastname: Chen
authors.affiliation: International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China; Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Han
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
authors.forename: Jingkao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nesi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Sestito
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6, 56126 Pisa, Italy. Electronic address: simona.rapposelli@farm.unipi.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.affiliation: School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China; National and Local United Engineering Lab of Drug Ability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: pirb@mail.sysu.edu.cn.
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Pi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques / Q000379:methods; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D000068836:Rivastigmine / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D003373:Coumaric Acids; D018696:Neuroprotective Agents; D000068836:Rivastigmine
keywords: Alzheimer's disease; Caffeic acid; Ferulic acid; Hybrid; Multifunctional agents; Rivastigmine