Pocket-based Lead Optimization Strategy for the Design and Synthesis of Chitinase Inhibitors

文献类型： 外文期刊

第一作者： Hu, Song

作者： Hu, Song;Ling, Yun;He, Xiongkui;Zhang, Li;Jiang, Xi;Liu, Tian;Yang, Qing;Yang, Qing

作者机构：

关键词： chitinase; lead optimization; inhibitors; pesticide; Ostrinia furnacalis

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： 2019 年 67 卷 13 期

页码：

收录情况： SCI

摘要： Insect chitinases play an indispensable role in shedding old cuticle during molting. Targeting chitinase inhibition is a promising pest control strategy. Of ChtI, a chitinase from the destructive insect pest Ostrinia furnacalis (Asian corn borer), has been suggested as a potential target for designing green pesticides. A 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate scaffold was previously obtained, and further derivatization generated the lead compound 1 as Of ChtI inhibitor. Here, based on the predicted binding mode of compound 1, the pocket-based lead optimization strategy was applied. A series of analogues was synthesized, and their inhibitory activities against Of ChtI were evaluated. Compound 8 with 6-tert-pentyl showed preferential inhibitory activity with a Ki value of 0.71 mu M. Their structureactivity relationships suggested that the compound with larger steric hindrance at the 6-nonpolar group was essential for inhibitory activity due to its stronger interactions with surrounding amino acids. This work provides a strategy for designing potential chitinase inhibitors.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序