Synthesis of potent neuroprotective butenolides based on plant smoke derived 3,4,5-Trimethylfuran-2(5H)-one and 3-methyl-2H-furo[2,3-c]pyrone-2-one

Phytochemistry. 2019 Jul:163:187-194. doi: 10.1016/j.phytochem.2019.03.014. Epub 2019 Apr 20.

Abstract

Smoke derived karrikinolide and trimethylbutenolide exerted neuroprotective effects against monoamine oxidase and acetylcholinesterase. Synthesis of potent analogs was achieved. Sulphur substitution in the bicyclic ring structure of KAR1 displayed the most encouraging activity returning IC50 values of 13.75 ± 0.001 μM and 0.03 ± 0.02 μM for monoamine oxidase A and B and 0.08 ± 0.006 μM for acetylcholinesterase. Neuroprotective butenolides may be particularly useful in the treatment of depressive disorders, Alzheimer's and Parkinson's diseases.

Keywords: Acetylcholinesterase; Karrikinolide; Monoamine oxidase; Smoke; Synthesis; Trimethylbutenolide.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • Acetylcholinesterase / metabolism
  • Depressive Disorder / drug therapy*
  • Dose-Response Relationship, Drug
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology*
  • Humans
  • Molecular Structure
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Neurodegenerative Diseases / drug therapy*
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Pyrans / chemical synthesis
  • Pyrans / chemistry
  • Pyrans / pharmacology*
  • Structure-Activity Relationship

Substances

  • 3,4,5-trimethylfuran-2(5H)-one
  • 3-methyl-2H-furo(2,3-c)pyran-2-one
  • Furans
  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents
  • Pyrans
  • butenolide
  • Monoamine Oxidase
  • Acetylcholinesterase
  • 4-Butyrolactone