Coordination Chemistry Based Approach to Lipophilic Inhibitors of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase
Coordination Chemistry Based Approach to Lipophilic Inhibitors of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase
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DOI：
10.1021/jm9012592
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发表时间：
2009-11-12
影响因子：
7.3
通讯作者：
Song, Yongcheng
中科院分区：
文献类型：
--
作者：
Deng, Lisheng;Sundriyal, Sandeep;Song, Yongcheng
大多数细菌中发现的非甲羟戊酸途径中的 1-脱氧-D-木酮糖-5-磷酸还原异构酶 (DXR) 是经过验证的抗感染药物靶点。 Fosmidomycin 是一种有效的 DXR 抑制剂，对革兰氏阴性菌具有活性。采用基于配位化学和结构的方法发现了一种新型亲脂性 DXR 抑制剂，IC50 为 1.4 μM。它对革兰氏阴性和阳性细菌具有广谱活性，最低抑制浓度为 20-100 μM（或 3.7-19 μg/mL）。
1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-negative bacteria. A coordination chemistry and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 mu M. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20-100 mu M (or 3.7-19 mu g/mL).