Screening Flavonoids for Inhibition of Acetylcholinesterase Identified Baicalein as the Most Potent Inhibitor

Azize Balkis, Khoa Tran, Yan Zhi Lee, Ken Ng

Abstract

Screening phenolic and polyphenolic compounds for inhibitory activity against electric eels acetylcholinesterase (AChE) identified baicalein, a major flavone derived from the roots ofScutellaria baicalensis, as the most potent inhibitor with IC50 (concentration required for 50% inhibition) of 0.61 μM. None of the hydroxybenzoic and hydroxycinnamic acids screened showed inhibitory activity measured at 100 μM. Structure-activity relationships based on IC50 values of the active flavonoids showed that inhibitory activity (a) required the unsaturated 2-phenyl-chroman structure, (b) has strong requirement for the A-ring A5-OH, A6-OH and A7-OH groups (b) does not depend on B-ring hydroxyl groups, and (d) was reduced by bulky sugar substitution of the saturated C-ring C3-OH. Enzyme kinetic analysis showed that baicalein is a mixed inhibitor of AChE with K1(equilibrium constant of dissociation of the inhibitor bound enzyme complex) and K2(equilibrium constant of dissociation of the inhibitor bound enzyme-substrate complex) of 0.91 and 1.98 μM, respectively.

 brevicornum leaves  were purchased from Chengdu Biopurify Pty. Ltd. (Chengdu, China).