Synthesis and evaluation of hydroxylated flavones and related compounds as potential inhibitors of the protein-tyrosine kinase p56lck.
An array of hydroxylated flavones and related compounds was synthesized and evaluated for inhibition of the in vitro protein-tyrosine kinase activity of p56lck, an enzyme that is thought to play a key role in mediating signal transduction from the CD4 receptor during lymphocyte activation. In general, the most active compounds had hydroxyl groups on both the A and C rings. At least two hydroxyl groups were required for good inhibitory activity, and the relative positions of these groups played an important role in determining potency. Compounds without hydroxyl groups were inactive as inhibitors.
Cushman
M
M
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Nagarathnam
D
D
Geahlen
R L
RL
D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology; D006900:Hydroxylation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D005419:Flavonoids; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)