Flavonoids and their derivatives with β-amyloid aggregation inhibitory activity from the leaves and twigs of Pithecellobium clypearia Benth

Abstract

To explore potential compounds with marked effect on Alzheimer's disease (AD) in Pithecellobium clypearia Benth., nineteen compounds (1-19) were obtained, including two new flavonoid derivatives, named pithecellobiumol A (1) and pithecellobiumol B (2) and 17 flavonoids (3-19). Their structures were elucidated based on 1D and 2D-NMR spectra as well as HR-ESI-MS data. The absolute configurations of new compounds were assigned by comparing their experimental specific rotation or ECD curves with the calculated data. The inhibitory activity on Aβ aggregation was screened by ThT assay, and compounds 7 (70.7%), 9 (86.5%), 10 (88.4%), 15 (86.1%) and 16 (87.7%) showed outstanding inhibition rate at 20μM compared to the positive control, curcumin (65.64%). In addition, docking study was performed to initially examine possible molecular mechanisms. Considering the important role of oxidative stress in AD, all the isolated compounds were tested for their H₂O₂-induced damage in human neuronblastoma SH-SY5Y cells. Among them, compound 16 (91.0%) was the most potent candidate in the treatment of AD.

Keywords: Aβ aggregation inhibition; Flavonoids; Molecular docking; Neuroprotective activity; P. clypearia.