Amaryllidaceae alkaloids from Narcissus pseudonarcissus L. cv. Dutch Master as potential drugs in treatment of Alzheimer's disease

Phytochemistry. 2019 Sep:165:112055. doi: 10.1016/j.phytochem.2019.112055. Epub 2019 Jun 28.

Abstract

Twenty-one known Amaryllidaceae alkaloids of various structural types and one undescribed alkaloid, named narcimatuline, have been isolated from fresh bulbs of Narcissus pseudonarcissus L. cv. Dutch Master. The chemical structures were elucidated by combination of MS, HRMS, 1D and 2D NMR spectroscopic techniques, and by comparison with literature data. Narcimatuline amalgamates two basic scaffolds of Amaryllidaceae alkaloids in its core, namely galanthamine and galanthindole. All isolated compounds were evaluated for their in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), prolyl oligopeptidase (POP), and glycogen synthase kinase-3β (GSK-3β) inhibitory activities. The most interesting biological profile was demonstrated by newly isolated alkaloid narcimatuline.

Keywords: Alkaloids; Alzheimer's disease; Amaryllidaceae; Cholinesterase inhibition; Glycogen synthase kinase-3β inhibition; Narcimatuline; Narcissus pseudonarcissus L. cv. Dutch master; Prolyl oligopeptidase.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amaryllidaceae Alkaloids / chemistry
  • Amaryllidaceae Alkaloids / isolation & purification
  • Amaryllidaceae Alkaloids / pharmacology*
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / isolation & purification
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Molecular Structure
  • Narcissus / chemistry*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Prolyl Oligopeptidases
  • Serine Endopeptidases / metabolism
  • Structure-Activity Relationship

Substances

  • Amaryllidaceae Alkaloids
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Glycogen Synthase Kinase 3 beta
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Serine Endopeptidases
  • PREPL protein, human
  • Prolyl Oligopeptidases