Thirteen known (1-12 and 16) and three previously undescribed Amaryllidaceae alkaloids of belladine structural type, named carltonine A-C (13-15), were isolated from bulbs of Narcissus pseudonarcissus 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 (hBUChE) inhibitory activity was demonstrated by newly described alkaloids carltonine A (13) and carltonine B (14) with IC50 values of 913 ± 20 nM and 31 ± 1 nM, respectively. Both compounds displayed a selective inhibition pattern for hBuChE 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 13 and 14 in the active site of hBuChE.

ADINACO Research Group Department of Pharmaceutical Botany Faculty of Pharmacy Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Biomedical Research Centre University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic

Department of Analytical Chemistry Faculty of Pharmacy Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Military Medical Service Organisation and Management Faculty of Military Health Sciences University of Defence Třebešská 1575 500 05 Hradec Králové Czech Republic

Department of Organic and Bioorganic Chemistry Faculty of Pharmacy Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Pharmacognosy Faculty of Pharmacy Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Toxicoloxy and Military Pharmacy Faculty of Military Health Sciences University of Defence Třebešská 1575 500 05 Hradec Králové Czech Republic

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