Synthesis and structure-activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity
Synthesis and structure-activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity
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DOI：
10.1016/j.bmc.2005.10.025
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发表时间：
2006-03-15
影响因子：
3.5
通讯作者：
Wiemer, DF
中科院分区：
文献类型：
--
作者：
Neighbors, JD;Salnikova, MS;Wiemer, DF
对几种对映体富集的 schweinfurthin B 类似物进行了合成和生物学评价，以开发结构-活性关系并指导其假定分子靶标的探针设计。所需的二苯乙烯含有常见的左半六氢呫吨环系统和具有不同取代基的芳族右半环系统。该合成涉及几种右半膦酸酯之一与包含 3-deoxyschweinfurthin B 左半部分的醛的倒数第二个 Horner-Wadsworth-Emmons 偶联。描述了所需膦酸酯和各自的二苯乙烯的制备，以及这些新化合物在国家癌症研究所 60 细胞系抗癌筛选中的细胞毒性特征。其中一些类似物表现出与天然产物良好相关的细胞毒性模式，并且在不同细胞系中的活性差异与 10(3) 类似。总之，这些测定结果表明至少一个游离酚基团油该系统的芳香族D-环对于差异细胞毒性的重要性。 (c) 2005 Elsevier Ltd. 保留所有权利。
The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure-activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner-Wadsworth-Emmons coupling of one of several right-half phosphonates with the aldehyde comprising the left-half of 3-deoxyschweinfurthin B. Preparation of the requisite phosphonates, and the respective stilbenes, as well as the cytotoxicity profiles of these new compounds in the National Cancer Institute's 60 cell-line anticancer screen is described. several of these analogs displayed cytotoxicity patterns well-correlated with the natural product and differences in activity of similar to 10(3) across the various cell lines. Together, these assay results indicate the importance of at least one free phenol group Oil the aromatic D-ring of this system for differential cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.