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首页> 外文期刊>Chemistry: A European journal >Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM Inhibitors
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Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM Inhibitors

机译：天然和合成的黄酮类黄酮是有效的结核菌UGM抑制剂

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摘要

This study reports a novel class of inhibitors of uridine 5'-diphosphate (UDP) galactopyranose mutase (UGM) derived from a screening of natural products. This enzyme is an essential biocatalyst involved in the cell wall biosynthesis of Mycobacterium tuberculosis. Flavonoids are potent inhibitors of UGM. The synthesis of novel methylated flavonoids allowed a structure-activity relationship analysis to be performed and which functional groups and structural elements were required for UGM inhibition could be determined. The binding mode of one of the best inhibitors was found to be noncompetitive. Docking simulations indicated that this molecule was likely to bind UGM in its open conformation, in a cavity recently identified as a "druggable" pocket. Importantly, two of the best inhibitors of the M. tuberculosis UGM displayed moderate activity against whole M. tuberculosis cells. This study reports the first natural products that act as inhibitor of UGM. Given the importance of natural products in medicinal chemistry, these results create new opportunities for the discovery of new antitubercular agents.
机译：本研究报告了衍生自天然产物筛选的尿苷5'-二磷酸（UDP）半乳糖糖烷（UGM）的新型抑制剂。该酶是参与细胞壁生物合成的必需生物催化剂的结核分枝杆菌。黄酮类化合物是UGM的有效抑制剂。新型甲基化的黄酮类化合物的合成允许进行结构 - 活性关系分析，并且可以确定UGM抑制所需的官能团和结构元素。发现其中一种最佳抑制剂的结合模式是非竞争力的。对接模拟表明该分子可能在其开放构象中结合UGM，在最近被识别为“可用的”口袋的腔中。重要的是，M.Tuberculosis UGM的两种最佳抑制剂患者对整个M.结核病细胞显示着适度的活性。本研究报告了作为UGM抑制剂的第一个天然产物。鉴于天然产品在药用化学中的重要性，这些结果为发现新的抗细胞剂创造了新的机会。

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  • 来源
    《Chemistry: A European journal》 |2017年第43期|共7页
  • 作者

    Sydney A. Villaume; Jian Fu; InHs NGo; Hui Liang; Huayong Lou; Laurent Kremer; Weidong Pan; Stéphane P. Vincent;

  • 作者单位

    Department of Chemistry University of Namur Rue de Bruxelles 61 5000 Namur (Belgium);

    Department of Chemistry University of Namur Rue de Bruxelles 61 5000 Namur (Belgium);

    Department of Chemistry University of Namur Rue de Bruxelles 61 5000 Namur (Belgium);

    Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University 3491 Baijin Road Guiyang 550014 (P. R. China);

    Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University 3491 Baijin Road Guiyang 550014 (P. R. China);

    IRIM (ex-CPBS)-UMR 9004 Infectious Disease Research Institute of Montpellier (IDRIM) Université de Montpellier CNRS 34293 Montpellier (France);

    Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University 3491 Baijin Road Guiyang 550014 (P. R. China);

    Department of Chemistry University of Namur Rue de Bruxelles 61 5000 Namur (Belgium);

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 应用化学;
  • 关键词

    allosterism; enzymes; inhibitors; natural products; structure-activity relationships;

    机译：颠振;酶;抑制剂;天然产品;结构 - 活动关系;

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