Synthesis and Biological Evaluation of Scutellarein Alkyl Derivatives as Preventing Neurodegenerative Agents with Improved Lipid Soluble Properties

Med Chem. 2019;15(7):771-780. doi: 10.2174/1573406414666181015143551.

Abstract

Background: Exogenous antioxidants are considered as a promising therapeutic approach to treat neurodegenerative diseases since they could prevent and/or minimize the neuronal damage by oxidation.

Objective: Three series of lipophilic compounds structurally based on scutellarein (2), which is one metabolite of scutellarin (1) in vivo, have been designed and synthesized.

Methods: Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes. The lipophilicity of these compounds indicated as partition coefficient between n-octanol and buffer was investigated by ultraviolet (UV) spectrophotometer.

Results: This study indicated that compound 5e which had a benzyl group substituted at the C4'- OH position showed a potent antioxidant activity and good lipophilicity.

Conclusion: 5e could be an effective candidate for preventing or reducing the oxidative status associated with the neurodegenerative processes.

Keywords: Alzhei-mer's disease; antioxidant; lipophilicity; neurodegenerative; scutellarein; scutellarin..

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Apigenin / chemical synthesis
  • Apigenin / chemistry
  • Apigenin / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Lipid Peroxidation / drug effects
  • Lipids / chemistry*
  • Molecular Structure
  • Neurodegenerative Diseases / drug therapy
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Solubility
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Lipids
  • Neuroprotective Agents
  • Apigenin
  • scutellarein