O-alkylated quercetins with selective acetylcholinesterase and beta-secretase inhibitions from Melicope glabra leaves, and their flavonols profile by LC-ESI-Q-TOF/MS

Abstract

Intensive investigation of phytochemicals from edible Melicope glabra leaves provided a series of O-alkylated quercetins (1-13). The quercetin 1 bearing prenyl and methyl motif showed potent inhibition to human acetylcholinesterase (hAChE) with mixed type I mode, while quercetin was inactive. The position of methyl group was also a critical factor to hAChE inhibition: 1 (4'-O-methyl, IC50 = 12.7 mu M) vs 2 (3'-O-methyl, IC50 = 119 mu M). Inhibitory potency was doubly confirmed with the binding affinity (K-SV) based on fluorescence quenching. O-Methyl groups on quercetin were observed to influence beta-secretase (BACE1) inhibition. Thus, O-methylated quercetins (4-6) displayed potential inhibitions against BACE1 with IC50 values of 1.3, 4.1, and 14.1 mu M, respectively. All compounds (3-6) have noncompetitive mode to BACE1. Additionally, all quercetin derivatives (1-13) had antioxidant potentials against different radical sources (ABTS, ORAC and FRAP). The UPLC-ESI-Q-TOF/MS indicated that the leaves part had promising metabolites towards hAChE and BACE1 inhibitions, which are the most predominant phytochemicals.