Thakkar K, Geahlen R L, Cushman M
Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Indiana 47907.
J Med Chem. 1993 Oct 1;36(20):2950-5. doi: 10.1021/jm00072a015.
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.
已制备了一系列与抗白血病天然产物反式-3,3',4,5'-四羟基芪（白皮杉醇）（1）相关的羟基化反式芪，并测试了它们对淋巴细胞系特异性蛋白酪氨酸激酶p56lck的抑制作用，该激酶在淋巴细胞增殖和免疫功能中起重要作用。相对于天然产物，许多类似物表现出增强的酶抑制活性。发现连接两个芳环的双键还原以及酚羟基的苄基化会显著降低活性。该系列中最有效的化合物证明是反式-3,3',5,5'-四羟基芪、反式-3,3',5-三羟基芪和反式-3,4,4'-三羟基芪。
