Plant phenolics as b-secretase (BACE1) inhibitors

Abstract

Various plant phenolics were assessed for b-secretase (BACE1) inhibitory activity in order to screen for anti-dementia agents. Among 39 phenolics, eight compds., 1,2,3-trigalloyl glucopyranoside, acetonyl geraniin, euphorscopin, furosine, helioscopinin A, helioscopinin B, jolkinin, and rugosin E exhibited strong inhibition of BACE1 with IC50 values of 5.87*10-8-54.93*10-6 M. Among them, rugosin E was the most potent (IC50 5.87*10-8 M). The active compds. were shown to be non-competitive inhibitors by Dixon plot. All the phenolic BACE1 inhibitors except furosin also suppressed prolyl endopeptidase (PEP) activity. However, these phenolic compds. caused less inhibition of a-secretase (tumor necrosis factor a converting enzyme; TACE) and no significant inhibition of other serine proteases such as trypsin, chymotrypsin, and elastase was seen, demonstrating that they are relatively specific to both BACE1 and PEP. No significant structure-activity relationships were found. [on SciFinder (R)]