SYNTHESIS AND PROTEIN-TYROSINE KINASE INHIBITORY ACTIVITY OF POLYHYDROXYLATED STILBENE ANALOGS OF PICEATANNOL
SYNTHESIS AND PROTEIN-TYROSINE KINASE INHIBITORY ACTIVITY OF POLYHYDROXYLATED STILBENE ANALOGS OF PICEATANNOL
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DOI：
10.1021/jm00072a015
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发表时间：
1993-10-01
影响因子：
7.3
通讯作者：
CUSHMAN, M
中科院分区：
文献类型：
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作者：
THAKKAR, K;GEAHLEN, RL;CUSHMAN, M
制备了一系列与抗白血病天然产物反式-3，3 '，4，5'-四羟基二苯乙烯（云杉醇）（1）相关的羟基化反式二苯乙烯，并测试了其对淋巴细胞谱系特异性蛋白酪氨酸激酶p56 lck的抑制作用，该蛋白酪氨酸激酶在淋巴细胞增殖和免疫功能中起重要作用。许多类似物显示出相对于天然产物增强的酶抑制活性。发现两个芳环的双键桥连的还原和酚羟基的苄基化显著降低活性。在该系列化合物中，最有效的化合物被证明是反式-3，3 '，5，5'-四羟基二苯乙烯、反式-3，3 '，5-三羟基二苯乙烯和反式-3，4，4'-三羟基二苯乙烯。
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.