Discovery of Biphenyl-Sulfonamides as Novel beta-N-Acetyl-D-Hexosaminidase Inhibitors via Structure-Based Virtual Screening

文献类型： 外文期刊

第一作者： Chen, Tao

作者： Chen, Tao;Liu, Zheng;Jiang, Wen;Zhu, Xiao-Lei;Yang, Guang-Fu;Li, Wen-Qin;Liu, Tian;Yang, Qing;Yang, Qing

作者机构：

关键词： beta-N-acetyl-D-hexosaminidase; Of Hex1; inhibitors; molecular docking virtual screening; biphenyl-sulfonamide

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.279； 五年影响因子：5.269 ）

ISSN： 0021-8561

年卷期： 2021 年 69 卷 40 期

页码：

收录情况： SCI

摘要： Novel insecticidal targets are always in demand due to the development of resistance. OfHex1, a beta-N-acetyl-D-hexosaminidase identified in Ostrinia furnacalis (Asian corn borer), is involved in insect chitin catabolism and has proven an ideal target for insecticide development. In this study, structure-based virtual screening, structure simplification, and biological evaluation are used to show that compounds with a biphenyl-sulfonamide skeleton have great potential as OfHex1 inhibitors. Specifically, compounds 10k, 10u, and 10v have K-i values of 4.30, 3.72, and 4.56 mu M, respectively, and thus, they are more potent than some reported nonglycosyl-based inhibitors such as phlegmacin B-1 (K-i = 26 mu M), berberine = 12 mu M), 2 (K-i = 11.2 mu M), and 3 (K-i = 28.9 mu M). Furthermore, inhibitory kinetic assessments reveal that the target compounds are competitive inhibitors with respect substrate, and based on toxicity predictions, most of them have potent drug properties. The obtained results indicate that the biphenyl-sulfonamide skeleton characterized by simple chemical structure, synthetic tractability, potent activity, and low toxicity has potential for further development in pest management targeting OfHex1.

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