Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits.

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Cho JK, Ryu YB, Curtis-Long MJ, Ryu HW, Yuk HJ, Kim DW, Kim HJ, Lee WS, Park KH

Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits.

Bioorg Med Chem. 2012 Apr 15;20(8):2595-602. doi: 10.1016/j.bmc.2012.02.044. Epub 2012 Mar 8.

PubMed ID

22445674 [ View in PubMed

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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 muM for hAChE and 1.4 muM 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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Physostigmine	Acetylcholinesterase	IC 50 (nM)	150	N/A	N/A	Details