N-Alkylated galanthamine derivatives: Potent acetylcholinesterase inhibitors from Leucojum aestivum.
N-(14-Methylallyl)norgalanthamine, a new natural compound, together with five known alkaloids: N-allylnorgalanthamine, galanthamine, epinorgalanthamine, narwedine, and lycorine were isolated from mother liquors (waste material) obtained after industrial production of galanthamine hydrobromide from Leucojum aestivum leaves. The structures of N-allylnorgalanthamine and N-(14-methylallyl)norgalanthamine were completely determined by (1)H and (13)C NMR spectroscopy and two-dimensional experiments. N-allylnorgalanthamine (IC(50)=0.18microM) and N-(14-methylallyl)norgalanthamine (IC(50)=0.16microM) inhibit AChE considerably more than the approved drug galanthamine (IC(50)=1.82microM).
Berkov
Strahil
S
Departament de Productes Naturals, Biologia Vegetal i Edafologia, Facultat de Farmàcia, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain.
Codina
Carles
C
Viladomat
Francesc
F
Bastida
Jaume
J
D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification; D000478:Alkylation; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D005702:Galantamine / Q000031:analogs & derivatives* / Q000302:isolation & purification; D020128:Inhibitory Concentration 50; D019668:Liliaceae / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010946:Plants, Medicinal / Q000737:chemistry*
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D005702:Galantamine