Inhibition of protein-tyrosine kinase activity by flavanoids and related compounds

J Nat Prod. Sep-Oct 1989;52(5):982-6. doi: 10.1021/np50065a011.

Abstract

A series of 22 flavanoids and related compounds were tested for their ability to inhibit the activity of a protein-tyrosine kinase purified from bovine thymocytes (p40). Flavones or flavanols with hydroxyl groups at C-5 and C-7 or with three hydroxyl groups on the phenyl ring were potent inhibitors of p40. The replacement of hydroxyl groups with methoxyl groups led to a substantial loss of inhibitory activity. The presence of methoxyl or rhamnosyl substituents at C-3 also abolished inhibitory activity. Kinetic analyses indicated that the flavone apigenin [2] was a competitive inhibitor of p40 with respect to ATP. Flavanones and isoflavones were relatively inactive as protein-tyrosine kinase inhibitors. The isoflavone genistein [17], which has been reported as a potent inhibitor of both pp60(v=src) and the epidermal growth factor receptor, was not an inhibitor of p40.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Flavonoids / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thymus Gland / cytology

Substances

  • Flavonoids
  • Protein-Tyrosine Kinases