Synthesis and protein-tyrosine kinase inhibitory activity of polyhydroxylated stilbene analogues of piceatannol.
A series of hydroxylated trans-stilbenes related to the antileukemic natural product trans-3,3',4,5'-tetrahydroxystilbene (piceatannol) (1) has been prepared and tested for inhibition of the lymphoid cell lineage-specific protein-tyrosine kinase p56lck, which plays an important role in lymphocyte proliferation and immune function. A number of the analogues displayed enhanced enzyme inhibitory activity relative to the natural product. Reduction of the double bond bridging the two aromatic rings and benzylation of the phenolic hydroxyl groups was found to decrease activity significantly. The most potent compounds in the series proved to be trans-3,3',5,5'-tetrahydroxystilbene, trans-3,3',5-trihydroxystilbene, and trans-3,4,4'-trihydroxystilbene.
Thakkar
K
K
Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Indiana 47907.
Geahlen
R L
RL
Cushman
M
M
D006900:Hydroxylation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008214:Lymphocytes / Q000201:enzymology*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010636:Phenols; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)