title: Design, synthesis and pharmacological evaluation of novel tacrine-caffeic acid hybrids as multi-targeted compounds against Alzheimer's disease.
abstract: A novel series of tacrine-caffeic acid hybrids (5a-f) were designed and synthesized by combining caffeic acid (CA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 5e showed the highest selectivity in inhibiting acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Enzyme kinetic study had suggested that 5e binds to both catalytic (CAS) and peripheral anionic sites (PAS) of AChE. Moreover, compound 5e also inhibited self- or AChE-induced β-amyloid(1-40) aggregation, as well as had potent neuroprotective effects against H(2)O(2)- and glutamate- induced cell death with low toxicity in HT22 cells.
authors.affiliation: Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chao
authors.forename: Xixin
authors.initials: X
authors.lastname: He
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yang
authors.forename: Xie
authors.initials: X
authors.lastname: Zhou
authors.forename: Minghua
authors.initials: M
authors.lastname: Jin
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Cheng
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianchen
authors.initials: J
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Pi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000378:metabolism; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013619:Tacrine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002109:Caffeic Acids; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D013619:Tacrine; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C040048:caffeic acid