Amino derivatives of platanic acid act as selective and potent inhibitors of butyrylcholinesterase

A set of thirtyfive 30-norlupan derivatives (2-36) was prepared from the natural triterpenoid platanic acid (PA), and the hydroxyl group at C-3, the carboxyl group at C-17 and the carbonyl group at C-20 were modified. These derivatives were tested for their inhibitory activity for the enzymes acetyicholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) using Ellman's assay. Extra enzyme kinetic studies were performed. The most active compound was (3 beta,20R)-3-acetyloxy-20-amino-30-norlupan-28-oate (32) showing a K-i value of 0.01 +/- 0.003 04 mu M for BChE. This compound proved to be a selective (F-B = 851), mixed-type inhibitor for BChE. (C) 2016 Elsevier Masson SAS. All rights reserved.