Two new minor Amaryllidaceae alkaloids were isolated from Hippeastrum × hybridum cv. Ferrari and Narcissus pseudonarcissus cv. Carlton. The chemical structures were identified by various spectroscopic (one- and two-dimensional (1D and 2D) NMR, circular dichroism (CD), high-resolution mass spectrometry (HRMS) and by comparison with literature data of similar compounds. Both isolated alkaloids were screened for their human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE) inhibition activity. One of the new compounds, a heterodimer alkaloid of narcikachnine-type, named narciabduliine (2), showed balanced inhibition potency for both studied enzymes, with IC50 values of 3.29 ± 0.73 µM for hAChE and 3.44 ± 0.02 µM for hBuChE. The accommodation of 2 into the active sites of respective enzymes was predicted using molecular modeling simulation.

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

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

Department of Analytical Chemistry Faculty of Pharmacy Charles University Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

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

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic

Department of Natural Drugs Faculty of Pharmacy Masaryk University Palackeho trida 1946 1 612 00 Brno Czech Republic

Department of Pharmacognosy Faculty of Pharmacy Charles University Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Department of Toxicology and Military Pharmacy University of Defence Trenesska 1575 500 05 Hradec Kralove Czech Republic

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Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer's Disease