title: Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl-benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids.
abstract: A series of berberine-phenyl-benzoheterocyclic (26-29) and tacrine-phenyl-benzoheterocyclic hybrids (44-46) were synthesised and evaluated as multifunctional anti-Alzheimer's disease agents. Compound 44b, tacrine linked with phenyl-benzothiazole by 3-carbon spacers, was the most potent AChE inhibitor with an IC(50) value of 0.017 μM. This compound demonstrated similar Aβ aggregation inhibitory activity with cucurmin (51.8% vs 52.1% at 20 μM, respectively), indicating that this hybrid is an excellent multifunctional drug candidate for AD.
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.forename: Wenjun
authors.initials: W
authors.lastname: Shan
authors.forename: Zonghua
authors.initials: Z
authors.lastname: Luo
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Xingshu
authors.initials: X
authors.lastname: Li
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001599:Berberine / Q000737:chemistry*; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002802:Cholinesterases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D013619:Tacrine / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D006571:Heterocyclic Compounds; D001599:Berberine; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases