Natural aristolactams and aporphine alkaloids as inhibitors of CDK1/cyclin B and DYRK1A

Molecules. 2013 Mar 6;18(3):3018-27. doi: 10.3390/molecules18033018.

Abstract

In an effort to find potent inhibitors of the protein kinases DYRK1A and CDK1/Cyclin B, a systematic in vitro evaluation of 2,500 plant extracts from New Caledonia and French Guyana was performed. Some extracts were found to strongly inhibit the activity of these kinases. Four aristolactams and one lignan were purified from the ethyl acetate extracts of Oxandra asbeckii and Goniothalamus dumontetii, and eleven aporphine alkaloids were isolated from the alkaloid extracts of Siparuna pachyantha, S. decipiens, S. guianensis and S. poeppigii. Among these compounds, velutinam, aristolactam AIIIA and medioresinol showed submicromolar IC50 values on DYRK1A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aporphines / chemistry
  • Aporphines / pharmacology*
  • CDC2 Protein Kinase / antagonists & inhibitors*
  • Cyclin B / antagonists & inhibitors*
  • Dyrk Kinases
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / pharmacology*
  • Lactams / chemistry
  • Lactams / pharmacology*
  • Nuclear Magnetic Resonance, Biomolecular
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*

Substances

  • Aporphines
  • Cyclin B
  • Indole Alkaloids
  • Lactams
  • Plant Extracts
  • aristolactam A
  • aristolactam BII
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase