Thiazolylhydrazone dervatives as inhibitors for insect N-acetyl-β-D-hexosaminidase and chitinase

作     者：Huibin Yang Huitang Qi Zesheng Hao Xusheng Shao Tian Liu Qing Yang Xuhong Qian Huibin Yang;Huitang Qi;Zesheng Hao;Xusheng Shao;Tian Liu;Qing Yang;Xuhong Qian

作者机构：Shanghai Key Laboratory of Chemical BiologyInstitute of Pesticides and PharmaceuticalsSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of the Discovery and Development of Novel PesticideShenyang Sinochem Agrochemicals Research and Development Co.Ltd.Shenyang 110021China School of BioengineeringDalian University of TechnologyDalian 116024China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2020年第31卷第5期

页      面：1271-1275页

核心收录：

学科分类：090403[农学-农药学(可授农学、理学学位）] 09[农学] 0904[农学-植物保护] 0703[理学-化学] 

基　　金：the National Key Research and Development Program of China(Nos.2017YFD0200500 2017YFD0201400 2018YFD0200100)for the financial support。 

主　　题：N-acetyl-β-D-hexosaminidase Chitinase Inhibitor Chitin Structure-activity relationship Thiazolylhydrazone derivatives Molecular docking 

摘      要：Insect chitinase and N-acetyl-β-D-hexosaminidases(Hex)are potential targets for developing new pesticides.Here,a series of thiazolylhydrazonesⅠ(with substituted group R1 at N3)andⅡ(with substituted group R1 at N2)were designed,synthesised and evaluated as competitive inhibitors of OfHexl and OfChi-h,from the agricultural pest Ostrinia furnacalis,DerivativesⅠ-3 d andⅡ-3 d,with phenoxyethyl group at R1,demonstrated the best inhibitory activities against OfHexl and OfChi-h.Molecular docking analysis indicated that the branched conformation compound II-3 d(Ki=1.5μmol/L)formed more hydrogen bonds with OfHexl than the stretched conformation compound I-3 d(Ki=5.9μmol/L).The differences in compounds’binding conformations with OfChi-h explained differences in inhibitory activity of compounds I-3 d(Ki=1.9μmol/L)and II-3 d(Ki=4.1μmol/L).This work suggests a novel scaffold for developing specific Hex and Chi-h inhibitors.