N-Alkylated galanthamine derivatives: Potent acetylcholinesterase inhibitors from Leucojum aestivum

Bioorg Med Chem Lett. 2008 Apr 1;18(7):2263-6. doi: 10.1016/j.bmcl.2008.03.008. Epub 2008 Mar 7.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / isolation & purification
  • Alkylation
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / isolation & purification
  • Galantamine / analogs & derivatives*
  • Galantamine / isolation & purification
  • Inhibitory Concentration 50
  • Liliaceae / chemistry*
  • Magnetic Resonance Spectroscopy
  • Plants, Medicinal / chemistry*

Substances

  • Alkaloids
  • Cholinesterase Inhibitors
  • Galantamine