Novel tacrine-ebselen hybrids with improved cholinesterase inhibitory, hydrogen peroxide and peroxynitrite scavenging activity.
A series of tacrine-ebselen hybrids were synthesised and evaluated as possible multifunctional anti-Alzheimer's disease (AD) agents. Compound 6i, which is tacrine linked with 5,6-dimethoxybenzo[d][1,2]selenazol-3(2H)-one by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitor, with IC50 values of 2.55 and 2.80 nM, respectively. Furthermore, this compound demonstrated similar hydrogen peroxide and peroxynitrite scavenging activity as ebselen by horseradish peroxidase assay and peroxynitrite scavenging activity assay, indicating that this hybrid is a good multifunctional drug candidate for the treatment of AD.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Fei
F
Mao
Jianwen
J
Chen
Qi
Q
Zhou
Zonghua
Z
Luo
Ling
L
Huang
Xingshu
X
Li
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001393:Azoles / Q000737:chemistry*; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006736:Horses; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D054833:Isoindoles; D007700:Kinetics; D062105:Molecular Docking Simulation; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013619:Tacrine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
C000589840:5,6-dimethoxy-2-(6-((1,2,3,4-tetrahydroacridin-9-yl)amino)hexyl)benzo(d)(1,2)selenazol-3(2H)-one; D001393:Azoles; D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D054833:Isoindoles; D016566:Organoselenium Compounds; D030421:Peroxynitrous Acid; C042986:ebselen; D013619:Tacrine; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
Alzheimer’s disease; Antioxidant; Cholinesterase inhibitor; Peroxynitrite scavenging activity