Coordination Chemistry Based Approach to Lipophilic Inhibitors of 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase

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• 作者：Lisheng Deng ; Sandeep Sundriyal ; Valentina Rubio ; Zheng-zheng Shi ; Yongcheng Song
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：November 12, 2009
• 年：2009
• 卷：52
• 期：21
• 页码：6539-6542
• 全文大小：811K
• 年卷期：v.52,no.21(November 12, 2009)
• ISSN：1520-4804

文摘

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 μM. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20−100 μM (or 3.7−19 μg/mL).