Design and synthesis of chitin synthase inhibitors as potent fungicides  

作　　者：Qi Chen Ji-Wei Zhang Lu-Lu Chen Jun Yang Xin-Ling Yang Yun Ling Qing Yang 

机构地区：[1]State Key Laboratory of Fine Chemical Engineering and School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China [2]Key Laboratory of Pesticide Chemistry and Application, Ministry of Agriculture, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China [3]Central Research Institute of China Chemical Science & Technology, Beijing 100083, China

出　　处：《Chinese Chemical Letters》2017年第6期1232-1237,共6页中国化学快报（英文版）

基　　金：supported by the Program for National Natural Science Funds for Distinguished Young Scholar(No.31425021);the National Natural Science Foundation of China(No.21472236);the Natural Science Foundation of Liaoning Province(No.2015020782);the Fundamental Research Funds for the Central Universities(No.DUT16TD22)

摘　　要：Chitin is a structural component of fungal cell walls but is absent in vertebrates,mammals,and humans.Chitin synthase is thus an attractive molecular target for developing fungicides.Based on the structure of its donor substrate,UDP-N-acetyl-glucosamine,as well as the modelled structure of the bacterial chitin synthase NodC,we designed a novel scaffold which was then further optimized into a series of chitin synthase inhibitors.The most potent inhibitor,compound 13,exhibited high chitin synthase inhibitory activity with an IC（50） value of 64.5 μmol/L All of the inhibitors exhibited antifungal activities against the growth of agriculturally-destructive fungi,Fusarium graminearum,Botrytis cinerea.and Colletotrichum lagenarium.This work presents a new scaffold which can be used for the development of novel fungicides.Chitin is a structural component of fungal cell walls but is absent in vertebrates,mammals,and humans.Chitin synthase is thus an attractive molecular target for developing fungicides.Based on the structure of its donor substrate,UDP-N-acetyl-glucosamine,as well as the modelled structure of the bacterial chitin synthase NodC,we designed a novel scaffold which was then further optimized into a series of chitin synthase inhibitors.The most potent inhibitor,compound 13,exhibited high chitin synthase inhibitory activity with an IC（50） value of 64.5 μmol/L All of the inhibitors exhibited antifungal activities against the growth of agriculturally-destructive fungi,Fusarium graminearum,Botrytis cinerea.and Colletotrichum lagenarium.This work presents a new scaffold which can be used for the development of novel fungicides.

关 键 词：Chitin synthase Inhibitor Fungicide UDP-N-acetyl-D-glucosamine 

分 类 号：TQ455[化学工程—农药化工]