'Click chemistry' synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against Trypanosoma cruzi and its cell surface trans-sialidase
'Click chemistry' synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against Trypanosoma cruzi and its cell surface trans-sialidase
复制标题
DOI：
10.1016/j.bmc.2010.02.053
复制
发表时间：
2010-04-01
影响因子：
3.5
通讯作者：
Field, Robert A.
中科院分区：
文献类型：
--
作者：
Carvalho, Ivone;Andrade, Peterson;Field, Robert A.
克氏锥虫转唾液酸酶（TcTS）在识别和入侵宿主细胞以及使寄生虫逃避人类免疫反应中起关键作用。为了探索这种潜在的药物靶点，我们合成了一个小型的底物类似物库，该库基于在C-1或C-6位置修饰的半乳糖的1，4-二取代的1，2，3-三唑衍生物。这是通过使用铜（I）催化的炔-叠氮化物环加成（CuAAC）反应将适当的叠氮基糖与一组23种结构不同的末端炔偶联来实现的，以良好至优异的产率和完全的区域选择性给出了46种衍生物的库。糖三唑类化合物在体外对TcTS催化的2 ′-（4-甲基伞形酮基）-α-D-N-乙酰神经氨酸水解有微弱的抑制作用（
Trypanosoma cruzi trans-sialidase (TcTS) plays a key role in the recognition and invasion of host cells and in enabling the parasite to escape the human immune response. To explore this potential drug target, we have synthesized a small library of substrate analogues based on 1,4-disubstituted 1,2,3-triazole derivatives of galactose modified at either the C-1 or C-6 positions. This was achieved by coupling the appropriate azido-sugars with a panel of 23 structurally diverse terminal alkynes by using the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, giving a library of 46 derivatives in good to excellent yield and with complete regioselectivity. The sugar triazoles showed weak inhibition towards TcTS-catalyzed hydrolysis of 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid in vitro (