title: O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation.
abstract: In an effort to identify novel multifunctional drug candidates for the treatment of Alzheimer's disease (AD), a series of hybrid molecules were synthesised by reacting N-(aminoalkyl)tacrine with salicylic aldehyde or derivatives of 2-aminobenzaldehyde. These compounds were then evaluated as multifunctional anti-Alzheimer's disease agents. All of the hybrids are potential biometal chelators, and in addition, most of them were better antioxidants and inhibitors of cholinesterases and amyloid-β (Aβ) aggregation than the lead compound tacrine. Compound 7c has the potential to be a candidate for AD therapy: it is a much better inhibitor of acetylcholinesterase (AChE) than tacrine (IC(50): 0.55 nM vs 109 nM), has good biometal chelation ability, is able to inhibit Aβ aggregation and has moderate antioxidant activity (1.22 Trolox equivalents).
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Zonghua
authors.initials: Z
authors.lastname: Luo
authors.forename: Anqiu
authors.initials: A
authors.lastname: Liu
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Lu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
authors.forename: Xingshu
authors.initials: X
authors.lastname: Li
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001596:Benzylamines / Q000737:chemistry* / Q000494:pharmacology*; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004593:Electrophorus; D006801:Humans; D008958:Models, Molecular; D013619:Tacrine / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001596:Benzylamines; D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D013619:Tacrine; C030796:benzylamine; D000110:Acetylcholinesterase