Citation: Chen Qi, Zhang Ji-Wei, Chen Lu-Lu, Yang Jun, Yang Xin-Ling, Ling Yun, Yang Qing. Design and synthesis of chitin synthase inhibitors as potent fungicides[J]. Chinese Chemical Letters, ;2017, 28(6): 1232-1237. doi: 10.1016/j.cclet.2017.03.030 shu

Design and synthesis of chitin synthase inhibitors as potent fungicides

Chen Qi ^a,1 ,
Zhang Ji-Wei ^b,c,1 ,
Chen Lu-Lu ^b ,
Yang Jun ^a ,
Yang Xin-Ling ^b ,
Ling Yun ^b,, ,
Yang Qing ^a,,

a.
State Key Laboratory of Fine Chemical Engineering and School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China
b.
Key Laboratory of Pesticide Chemistry and Application, Ministry of Agriculture, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China
c.
Central Research Institute of China Chemical Science & Technology, Beijing 100083, China

Corresponding author: Ling Yun, lyun@cau.edu.cn Yang Qing, qingyang@dlut.edu.cn

Received Date: 17 February 2017
Revised Date: 19 March 2017
Accepted Date: 21 March 2017
Available Online: 24 June 2017

Figures(3)

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 IC₅₀ 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 synthase,
- Inhibitor,
- Fungicide,
- UDP-N-acetyl-D-glucosamine
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