Synthesis of natural product-like polyprenylated phenols and quinones: Evaluation of their neuroprotective activities

Bioorg Med Chem. 2020 Jan 1;28(1):115156. doi: 10.1016/j.bmc.2019.115156. Epub 2019 Nov 8.

Abstract

Twenty-seven natural product-like polyprenylated phenols and quinones were synthesized and their neuroprotective activity was tested using human monoamine oxidase B (MAO-B) and SH-SY5Y cells. Eight compounds inhibited MAO-B (IC50 values < 25 μM) and the inhibition mode and molecular docking of two (8c and 16c) were investigated. Compounds inhibiting MAO-B activity were additionally tested for their ability to protect SH-SY5Y cells from peroxide injury. Three derivatives (3c, 8c and 16c) exhibited both MAO-B inhibitory and neuroprotective activity. A structure activity-relationship study showed that a phenolic hydroxyl group and a longer side chain are important for both activities.

Keywords: Derivatization; Fungal metabolites; MAO-B; Neogrifolin; SH-SY5Y cells.

MeSH terms

  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / pharmacology
  • Molecular Structure
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Quinones / chemical synthesis
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Biological Products
  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents
  • Phenols
  • Quinones
  • Hydrogen Peroxide
  • Monoamine Oxidase