title: Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.
abstract: A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7μM) and self-induced β-amyloid (Aβ1-42) aggregation (30.8-39.1%, 25μM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2μM), and Aβ1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Aβ aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD.
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Pan
authors.affiliation: Nanyang City Center Hospital, Nanyang 473061, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.affiliation: West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Bai
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Yu
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
authors.forename: Qinge
authors.initials: Q
authors.lastname: Ma
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
authors.forename: Changzhong
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
authors.forename: Kelin
authors.initials: K
authors.lastname: Peng
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China. Electronic address: liuwm1969@163.com.
authors.forename: Wenmin
authors.initials: W
authors.lastname: Liu
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China. Electronic address: sangzhipei@163.com.
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Sang
mesh_terms: D000473:Alkanes / Q000737:chemistry / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001812:Blood-Brain Barrier; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005021:Ethylamines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
chemical_list: D000473:Alkanes; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D003373:Coumaric Acids; D005021:Ethylamines; D018696:Neuroprotective Agents; C521476:memoquin; C004999:ferulic acid; D006861:Hydrogen Peroxide
keywords: AChE inhibitor; Alzheimer’s disease; Antioxidant; Aβ aggregation inhibitor; Hybrids; Neuroprotectant