Glycosyl triazoles as novel insect beta-N-acetylhexosaminidase OfHex1 inhibitors: Design, synthesis, molecular docking and MD simulations

文献类型： 外文期刊

第一作者： Shen, Shengqiang

作者： Shen, Shengqiang;Lu, Huizhe;Xu, Dongdong;Jin, Shuhui;Zhang, Jianjun;Chen, Wei;Yang, Qing;Yang, Qing

作者机构：

关键词： beta-N-acetyl-D-hexosaminidase; OfHex1; Glycosyl triazoles; Enzyme inhibitors; Molecular docking; MD simulations

期刊名称：BIOORGANIC & MEDICINAL CHEMISTRY （ 影响因子：3.641； 五年影响因子：3.319 ）

ISSN： 0968-0896

年卷期： 2019 年 27 卷 12 期

页码：

收录情况： SCI

摘要： The insect enzyme GH20 beta-N-acetyl-D-hexosaminidase OfHex1 represents an important chitinolytic enzyme found in the agricultural pest Ostrinia furnacalis (Guenee) and inhibition of this enzyme has been considered a promising strategy for the development of eco-friendly pesticides. In this article, based on the structure of the catalytic domains of OfHex1, a series of novel glycosyl triazoles were designed and synthesized via Cu-catalyzed azide-alkyne [3+ 2] cycloaddition reaction. To investigate the potency and selectivity of these glycosyl triazoles, the inhibition activities towards OfHex1 and HsHexB (human beta-N-acetylhexosaminidase B) were studied. Particularly compound 17c (OfHex1, K-i= 28.68 mu M; HsHexB, K-i > 100 mu M) exhibited a suitable activity and selectivity against OfHex1. Furthermore, the possible inhibitory mechanisms of 17c with OfHex1 were studied using molecular docking and MD simulations. The structure-activity relationship results as well as the formed binding patterns may provide promising insights into the further development of novel OfHex1 inhibitors.

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