N-acylanthranilic acid derivatives with anti-Aβ1-42 aggregation activity from the leaves of Isatis indigotica fortune

Fitoterapia. 2018 Jul:128:169-174. doi: 10.1016/j.fitote.2018.05.025. Epub 2018 May 19.

Abstract

Seven new N-acylanthranilic acid derivatives (1-3, 4a/4b, 5a/5b) including two pairs of enantiomers (4a/4b and 5a/5b) were isolated from the leaves of Isatis indigotica Fortune. Their chemical structures were elucidated by extensive spectroscopic data analyses. The absolute configurations of compounds 4a/4b and 5a/5b were determined by comparison of the experimental and calculated ECD spectra. All compounds were tested for their anti-Aβ1-42 aggregation activity. As a result, compounds 1 (72.1%), 2 (79.8%) and 5a (81.8%) showed stronger inhibitory activity than the positive control curcumin (67.0%). By the comparison between 5a (81.8%) and 5b (63.1%), it was found that stereochemical configurations may affect Aβ1-42 aggregation activity, which was discussed through the molecular docking results of compounds 5a and 5b.

Keywords: Anti-Aβ(1–42) aggregation; Isatis indigotica fort.; N-acylanthranilic acid derivatives.

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Isatis / chemistry*
  • Molecular Docking Simulation
  • Peptide Fragments / antagonists & inhibitors*
  • Plant Leaves / chemistry*
  • Stereoisomerism
  • ortho-Aminobenzoates / isolation & purification*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • ortho-Aminobenzoates