Synthesis, antioxidant and Aβ anti-aggregation properties of new ferulic, caffeic and lipoic acid derivatives obtained by the Ugi four-component reaction

Bioorg Chem. 2019 Apr:85:221-228. doi: 10.1016/j.bioorg.2018.12.029. Epub 2018 Dec 21.

Abstract

We report herein the synthesis antioxidant and Aβ anti-aggregation capacity of (E)-N-benzyl-N-[2-(benzylamino)-2-oxoethyl]-3-(aryl)acrylamides and related (R)-N-benzyl-N-(2-(benzylamino)-2-oxoethyl)-5-(1,2-dithiolan-3-yl)pentanamides 1-12. These compounds have been obtained, via Ugi four-component reaction, from modest to good yields. Their antioxidant analysis, using the DPPH and ORAC assays, allowed us to identify compounds 8 and 9, as potent antioxidant agents, showing also strong Aβ1-40 self-aggregation inhibition, two biological properties of interest in pathologies linked to the oxidative stress, such as Alzheimer's disease.

Keywords: (R)-Lipoic acid; Antioxidants; Aβ(1−40) self-aggregation inhibition; Benzyl isocyanide; Benzylamine; Caffeic acid; Ferulic acid; Multicomponent reactions; Ugi four-component reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Caffeic Acids / chemical synthesis
  • Caffeic Acids / chemistry
  • Caffeic Acids / pharmacology*
  • Cell Line, Tumor
  • Coumaric Acids / chemical synthesis
  • Coumaric Acids / chemistry
  • Coumaric Acids / pharmacology*
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Molecular Structure
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Peptide Fragments / metabolism
  • Protein Multimerization / drug effects*
  • Structure-Activity Relationship
  • Thioctic Acid / analogs & derivatives*
  • Thioctic Acid / chemical synthesis
  • Thioctic Acid / chemistry
  • Thioctic Acid / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Caffeic Acids
  • Coumaric Acids
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • Thioctic Acid
  • ferulic acid
  • Hydrogen Peroxide