Inhibition of protein-tyrosine kinase activity by flavanoids and related compounds.
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.
Geahlen
R L
RL
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana.
Koonchanok
N M
NM
McLaughlin
J L
JL
Pratt
D E
DE
D000818:Animals; D002417:Cattle; D005419:Flavonoids / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000166:cytology
D005419:Flavonoids; D011505:Protein-Tyrosine Kinases