Clinanthus microstephium, an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure-Activity Analysis of Haemanthamine Skeleton Derivatives

Chem Biodivers. 2019 May;16(5):e1800662. doi: 10.1002/cbdv.201800662. Epub 2019 Apr 9.

Abstract

Plants of the Amaryllidaceae family are well-known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR. Seven known compounds belonging to three structural types of Amaryllidaceae alkaloids were identified. An epimeric mixture of a haemanthamine-type compound (6-hydroxymaritidine) was tested as an inhibitor against acetyl- and butyrylcholinesterase enzymes (AChE and BChE, respectively), two enzymes relevant in the treatment of Alzheimer's disease, with good results. Structure-activity relationships through molecular docking studies with this alkaloid and other structurally related compounds were discussed.

Keywords: Amaryllidaceae; Clinanthus microstephium; alkaloids; biological activity; cholinesterase inhibitors; structure−activity relationship.

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Alkaloids / chemistry*
  • Alkaloids / metabolism
  • Alkaloids / pharmacology
  • Amaryllidaceae / chemistry*
  • Amaryllidaceae / metabolism
  • Amaryllidaceae Alkaloids / chemistry*
  • Binding Sites
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / isolation & purification
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology
  • Gas Chromatography-Mass Spectrometry
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Phenanthridines / chemistry*
  • Plant Extracts / chemistry
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Amaryllidaceae Alkaloids
  • Cholinesterase Inhibitors
  • Phenanthridines
  • Plant Extracts
  • hemanthamine
  • Acetylcholinesterase
  • Butyrylcholinesterase