Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits = 오동나무 열매로부터 분리한 geranylated 플라보노이드의 cholinesterase 저해활성

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 inhibitoryflavonoids (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 50s 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.