Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs
Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs
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DOI：
10.1021/jm010854
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发表时间：
2001-10-11
影响因子：
7.3
通讯作者：
Gilbert, IH
中科院分区：
文献类型：
--
作者：
Klenke, B;Stewart, M;Gilbert, IH
P2转运蛋白是一种核苷转运蛋白，是原虫原虫布氏锥虫所特有的，布氏锥虫是人类非洲锥虫病的病原体。转运蛋白被证明结合了一些其他转运蛋白不识别的结构基序。在这篇文章中，我们描述了三聚氰胺基序的使用，P2转运蛋白的底物，作为一种潜在的工具，选择性地向寄生虫输送多胺类似物。描述了一系列与各种三聚氰胺类似物相连的多胺类似物的合成。许多化合物被证明竞争性地抑制腺苷的摄取，这表明它们被转运蛋白识别。部分化合物表现出良好的体外抗寄生虫活性。
The P2 transporter is a nucleoside transporter which is unique to the protozoan parasite Trypanosoma brucei, the causative organism of Human African Trypanosomasis. The transporter has been shown to bind some structural motifs not recognized by other transporters. In this paper we describe the use of the melamine motif, a substrate of the P2 transporter, as a potential tool to selectively deliver polyamine analogues to the parasites. The synthesis of a number of polyamine analogues attached to a variety of melamine analogues is described. Many of the compounds were shown to competitively inhibit uptake of adenosine, indicating that they are recognized by the transporter. Some of the compounds showed good in vitro activity against the parasites.