Discovery of dihydrobenzofuran neolignans from Rubus ideaus L. with enantioselective anti-Aβ1-42 aggregation activity

Bioorg Chem. 2018 Oct:80:64-69. doi: 10.1016/j.bioorg.2018.05.016. Epub 2018 May 30.

Abstract

Four new dihydrobenzofuran neolignans 1a/1b and 2a/2b were isolated from the fruit of Rubus ideaus. 1a/1b and 2a/2b as two pairs of enantiomers were separated on a chiral chromatographic column. Their structures were determined using a suite of techniques including 1D and 2D NMR, HRESIMS, together with theoretical electronic circular dichroism (ECD) calculation. All compounds were evaluated for their inhibition of self-induced Aβ1-42 aggregation. Compounds 1b and 2a exhibited optimal Aβ1-42 aggregation inhibition capability, with an inhibition potency of 81.6% and 83.4% at 20 μM, respectively. Additionally, molecular docking was performed to identify the possible factor responsible for the enantioselectivity in the anti-Aβ1-42 aggregation activity.

Keywords: Aβ(1–42) aggregation; Dihydrobenzofuran neolignans; Enantioselectivity; Rubus ideaus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism*
  • Benzofurans / chemistry*
  • Binding Sites
  • Circular Dichroism
  • Fruit / chemistry
  • Fruit / metabolism
  • Lignans / chemistry*
  • Lignans / isolation & purification
  • Lignans / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Molecular Docking Simulation
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / metabolism*
  • Plant Extracts / chemistry
  • Protein Structure, Tertiary
  • Rubus / chemistry*
  • Rubus / metabolism
  • Stereoisomerism

Substances

  • Amyloid beta-Peptides
  • Benzofurans
  • Lignans
  • Peptide Fragments
  • Plant Extracts
  • amyloid beta-protein (1-42)
  • benzofuran