Synthesis and biological activity of (±)-7,3',4'-trihydroxyhomoisoflavan and its analogs

Bioorg Med Chem Lett. 2021 Jan 1:31:127674. doi: 10.1016/j.bmcl.2020.127674. Epub 2020 Nov 6.

Abstract

Acetylcholinesterase (AChE) inhibitors and neurite outgrowth promoters are thought to alleviate the symptoms of degenerative brain disorders, such as Alzheimer's disease. We designed and synthesized a series of homoisoflavonoids based on the structure of natural homoisoflavan isolated from Dracaena cambodiana dragon's blood. The homoisoflavonoids were then evaluated as AChE inhibitors and neurite outgrowth promoters. The catechol structure of the homoisoflavan B rings was important for AChE inhibition, and some of the homoisoflavonoids significantly promoted neurite outgrowth induced by nerve growth factor (NGF).

Keywords: AChE inhibitory activity; Dracaena cambodiana; Dragon’s blood; Homoisoflavan; Neurite outgrowth promoting activity.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Dracaena / chemistry
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Nerve Growth Factors / metabolism
  • Neurites / drug effects*
  • Neurites / metabolism
  • PC12 Cells
  • Rats
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Nerve Growth Factors
  • Acetylcholinesterase