Amaryllidaceae Alkaloids of Belladine-Type from cv. Carlton as New Selective Inhibitors of Butyrylcholinesterase.

Thirteen known (- and ) and three previously undescribed Amaryllidaceae alkaloids of belladine structural type, named carltonine A-C (-), were isolated from bulbs of cv. Carlton (Amaryllidaceae) by standard chromatographic methods. Compounds isolated in sufficient amounts, and not tested previously, were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8) and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human BuChE (BUChE) inhibitory activity was demonstrated by newly described alkaloids carltonine A () and carltonine B () with IC values of 913 ± 20 nM and 31 ± 1 nM, respectively. Both compounds displayed a selective inhibition pattern for BuChE with an outstanding selectivity profile over AChE inhibition, higher than 100. The in vitro data were further supported by in silico studies of the active alkaloids and in the active site of BuChE.