title: Interaction study of two diterpenes, cryptotanshinone and dihydrotanshinone, to human acetylcholinesterase and butyrylcholinesterase by molecular docking and kinetic analysis.
abstract: Alzhemier's disease (AD) is a common form of dementia in the ageing population which is characterized by depositions of amyloids and a cholinergic neurotransmission deficit in the brain. Current therapeutic intervention for AD is primarily based on the inhibition of brain acetylcholinesterase (AChE) to restore the brain acetylcholine level. Cryptotanshinone (CT) and dihydrotanshinone (DT) were diterpenoids extracted from Salvia miltiorrhiza Bge. having anti-cholinesterase activity. Here we characterized the inhibition property of these two diterpenoids towards human AChE and butyrylcholinesterase (BChE). Both CT and DT were found to be mixed non-competitive inhibitors for human AChE and an uncompetitive inhibitor for human BChE. The docking analyses of CT and DT into the active sites of both cholinesterases indicate that they interact with the allosteric site inside the active-site gorge mainly by hydrophobic interactions.
authors.affiliation: The School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Kelvin Kin-Kwan
authors.initials: KK
authors.lastname: Wong
authors.forename: Jacky Chi-Ki
authors.initials: JC
authors.lastname: Ngo
authors.forename: Sijie
authors.initials: S
authors.lastname: Liu
authors.forename: Huang-Quan
authors.initials: HQ
authors.lastname: Lin
authors.forename: Chun
authors.initials: C
authors.lastname: Hu
authors.forename: Pang-Chui
authors.initials: PC
authors.lastname: Shaw
authors.forename: David Chi-Cheong
authors.initials: DC
authors.lastname: Wan
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004365:Drugs, Chinese Herbal; D006801:Humans; D008958:Models, Molecular; D010616:Phenanthrenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D027561:Salvia miltiorrhiza; D017386:Sequence Homology, Amino Acid
chemical_list: D002800:Cholinesterase Inhibitors; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D010618:Phenanthrolines; C028972:dan-shen root extract; C037886:cryptotanshinone; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase