The synthesis and inhibitory activity of dethiotrypanothione and analogues against trypanothione reductase.
The synthesis and inhibitory activity of dethiotrypanothione and analogues against trypanothione reductase.
复制标题
脱硫锥硫酮及其类似物的合成及其对锥硫酮还原酶的抑制活性。
DOI：
10.1021/jo062597s
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Alberg,DavidG
中科院分区：
文献类型：
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作者：
Czechowicz,JosephineA;Wilhelm,AprilK;Spalding,MaroyaD;Larson,AnnaM;Engel,LinneaK;Alberg,DavidG
锥硫酮还原酶（TR）催化二硫化物锥硫酮的NADPH依赖性还原（1）。TR在锥虫寄生虫防御氧化应激中起着核心作用，并已成为抗锥虫药物的一个有前途的靶点。我们描述了作为克氏锥虫TR抑制剂的脱硫锥硫酮及其类似物（2−4）的合成和活性。这些大环化合物的合成以钌催化剂催化的闭环烯烃复分解（RCM）反应为特征17。Derivative4是我们最有效的抑制剂，阿基= 16 μM。
Trypanothione reductase (TR) catalyzes the NADPH-dependent reduction of trypanothione disulfide (1). TR plays a central role in the trypanosomatid parasite's defense against oxidative stress and has emerged as a promising target for antitrypanosomal drugs. We describe the synthesis and activity of dethiotrypanothione and analogues (2−4) as inhibitors ofTrypanosoma cruziTR. The syntheses of these macrocycles feature ring-closing olefin metathesis (RCM) reactions catalyzed by ruthenium catalyst17. Derivative4is our most potent inhibitor with aKi= 16 μM.