title: Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits.
abstract: Alzheimer's disease is rapidly becoming one of the most prevalent human diseases. Inhibition of human acetylcholinestrase (hAChE) and butyrylcholinestrase (BChE) has been linked to amelioration of Alzheimer's symptoms and research into inhibitors is of critical importance. Purification of the methanol extract of Paulownia tomentosa fruits yielded potent hAChE and BChE inhibitory flavonoids (1-9). A comparative activity screen indicated that a geranyl group at C6 is crucial for both hAChE and BChE. For example, diplacone (8) showed 250-fold higher efficacy than its parent eriodictyol (12). IC(50)s of diplacone (8) were 7.2 μM for hAChE and 1.4 μM for BChE. Similar trends were also observed for 4'-O-methyldiplacone (4) (vs its parent, hesperetin 10) and mimulone (7) (vs its parent, naringenin 11). Representative inhibitors (1-8) showed mixed inhibition kinetics as well as time-dependent, reversible inhibition toward hAChE. The binding affinities of these compounds to hAChE were investigated by monitoring quenching of inherent enzyme fluorescence. The affinity constants (K(SA)) increased in proportion to inhibitory potencies.
authors.affiliation: Division of Applied Life Science (BK21 Program), IALS, Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Jung Keun
authors.initials: JK
authors.lastname: Cho
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Curtis-Long
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.forename: Dae Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D002802:Cholinesterases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D028083:Scrophulariaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D010936:Plant Extracts; D002802:Cholinesterases