Polypropionate Derivatives with Mycobacterium tuberculosis Protein Tyrosine Phosphatase B Inhibitory Activities from the Deep-Sea-Derived Fungus Aspergillus fischeri FS452
Polypropionate Derivatives with Mycobacterium tuberculosis Protein Tyrosine Phosphatase B Inhibitory Activities from the Deep-Sea-Derived Fungus Aspergillus fischeri FS452
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DOI：
10.1021/acs.jnatprod.9b00834
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发表时间：
2019-12-01
影响因子：
5.1
通讯作者：
Zhang, Weimin
中科院分区：
文献类型：
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作者：
Liu, Zhaoming;Wang, Qjnglin;Zhang, Weimin
渔丙酸酯A-F(1-6)是从深海真菌FS452中分离得到的六种新的聚丙酸酯衍生物，具有异常长的疏水链。通过光谱分析确定了它们的结构，并用J-HMBC分析、电子圆二色谱(ECD)计算和改进的Mosher方法确定了它们的绝对构型。这是首次从海洋来源的真菌中发现聚丙酸酯，化合物4和5代表了聚丙酸酯衍生物的第一个例子，其中包含3-羟基哌啶-2-酮作为亚胺键的一部分。此外，化合物1-4对结核分枝杆菌蛋白酪氨酸磷酸酶B(MptpB)表现出明显的抑制活性，其ICso分别为5.1、12、4.0和11mU M。酶动力学实验表明它们都是通过非竞争性机制起作用的。讨论了初步的构效关系。
Fiscpropionates A-F (1-6), six new polypropionate derivatives featuring an unusual long hydrophobic chain, were isolated from the deep -sea-derived fungus Aspergillus fischeri FS452. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were determined by J-HMBC analysis, electronic circular dichroism (ECD) calculations, and the modified Mosher's method. This is the first discovery of polypropionates from marine -derived fungi, and compounds 4 and 5 represent the first examples of polypropionate derivatives containing a 3-hydroxypiperidin-2-one as part of an imide linkage. In addition, compounds 1-4 exhibited significant inhibitory activities against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the ICso values of 5.1, 12, 4.0, and 11 mu M, respectively. Enzyme kinetic experiments suggested that they all acted through a noncompetitive mechanism. A preliminary structure activity relationship is discussed.