Synthesis, biological evaluation, and NMR studies of 3-fluorinated derivatives of 3',4',5'-trihydroxyflavone and 3',4',5'-trimethoxyflavone

Bioorg Med Chem Lett. 2021 Jan 15:32:127720. doi: 10.1016/j.bmcl.2020.127720. Epub 2020 Nov 28.

Abstract

Flavones are valuable scaffolds in medicinal chemistry, especially as they display activity as antioxidants and neuroprotective agents. The need to incorporate a fluorine atom on flavones has driven much of the recent synthetic work in this area. We now report a route for the production of 3-fluorinated derivatives of 3',4',5'-trihydroxyflavone and 3',4',5'-trimethoxyflavone. Biological evaluation of these agents, along with their non-fluorinated counterparts, demonstrate that antioxidant activity may be enhanced whereas neuroprotective activity is conserved. Also, the 3-fluoro-3',4',5'-trihydroxyflavone can act as an NMR probe to detect structural changes during its action as a radical scavenger.

Keywords: Antioxidant; Flavone; Fluorine; NMR; Neuroprotection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Cell Survival / drug effects
  • Flavones / chemical synthesis*
  • Flavones / chemistry
  • Flavonoids / chemistry*
  • Halogenation
  • Magnetic Resonance Spectroscopy
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology
  • Neurotoxins / pharmacology
  • Rats
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Flavones
  • Flavonoids
  • Neuroprotective Agents
  • Neurotoxins
  • Reactive Oxygen Species
  • 3',4',5'-trimethoxyflavone