Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase
Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase
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DOI：
10.1021/ml400259d
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Boxer, Matthew B.
中科院分区：
文献类型：
--
作者：
Brimacombe, Kyle R.;Walsh, Martin J.;Boxer, Matthew B.
人类非洲锥虫病(HAT)是由原虫布氏锥虫引起的一种严重的、往往是致命的疾病。糖酵解途径已被确定为这些生物感染阶段产生ATP的唯一机制，几种糖酵解酶，特别是磷酸果糖激酶(PFK)，已显示出作为潜在药物靶点的前景。在这里，我们描述了一种新型的布鲁氏毛滴虫PFK纳米分子抑制剂ML251的发现，以及该系列化合物的构效关系。
Human African Trypanosomiasis (HAT) is a severe, often fatal disease caused by the parasitic protist Trypanosoma brucei. The glycolytic pathway has been identified as the sole mechanism for ATP generation in the infective stage of these organisms, and several glycolytic enzymes, phosphofructokinase (PFK) in particular, have shown promise as potential drug targets. Herein, we describe the discovery of ML251, a novel nanomolar inhibitor of T. brucei PFK, and the structure-activity relationships within the series.