Design, synthesis and initial biological evaluation of a novel pladienolide analog scaffold
Design, synthesis and initial biological evaluation of a novel pladienolide analog scaffold
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DOI：
10.1039/c1md00040c
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发表时间：
2011-09-01
期刊：
影响因子：
--
通讯作者：
Webb, Thomas R.
中科院分区：
文献类型：
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作者：
Gundluru, Mahesh Kumar;Pourpak, Alan;Webb, Thomas R.
根据公认的药效团假说，设计了一种基于二烯内酯的新型、简化的合成支架。合成并评价了初始目标，以考察3-羟基和存在于1的10、16、20、22位的甲基对生物活性的作用。我们报道了第一个显示生物活性的完全合成的大环内酯类似物。我们的新合成策略使我们能够快速合成其他新的普拉二烯内酯类似物，以开发选择性的抗癌先导化合物。
A novel and simplified synthetic scaffold based on pladienolide was designed using a consensus pharmacophore hypothesis. An initial target was synthesized and evaluated to examine the role of the 3-hydroxy group and the methyl groups present at positions 10, 16, 20, 22 in 1, on biological activity. We report the first totally synthetic analog of this macrolide that shows biological activity. Our novel synthetic strategy enables the rapid synthesis of other new analogs of pladienolide in order to develop selective anticancer lead compounds.