Synthesis of ureido thioglycosides as novel insect beta-N-acetylhexosaminidase OfHex1 inhibitors

文献类型： 外文期刊

第一作者： Shen, Shengqiang

作者： Shen, Shengqiang;Dong, Lili;Lu, Huizhe;Dong, Yanhong;Zhang, Jianjun;Yang, Qing;Yang, Qing

作者机构：

关键词： Ureido thioglycosides; Trichloroethoxycarbonyl (Troc); beta-N-acetylhexosaminidase; OfHex1; Inhibitors

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： 2020 年 28 卷 15 期

页码：

收录情况： SCI

摘要： The insect beta-N-acetylhexosaminidase OfHex1 from Ostrinia furnacalis (one of the most destructive agricultural pests) has been considered as a promising pesticide target. In this study, a series of novel and readily available ureido thioglycosides were designed and synthesized based on the catalytic mechanism and the co-crystal structures of OfHex1 with substrates. After evaluation via enzyme inhibition experiments, thioglycosides 11c and 15k were found to have inhibitory activities against OfHex1 with the K-i values of 25.6 mu M and 53.8 mu M, respectively. In addition, all these ureido thioglycosides exhibited high selectivity toward OfHex1 over hOGA and HsHexB (K-i > 100 mu M). Furthermore, to investigate the inhibitory mechanism, the possible binding modes of 11c and 15k with OfHex1 were deduced based on molecular docking analysis. This work may provide useful structural starting points for further rational design of potent inhibitors of OfHex1.

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