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论文类型：期刊论文

发表时间：2018-04-04

发表刊物：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录刊物：PubMed、SCIE、EI

卷号：66

期号：13

页面范围：3351-3357

ISSN号：0021-8561

关键字：chitinase; inhibitors; fragment; structure-based virtual screening; structure-activity relationship

摘要：Chitinases play a vital part in the molting phase of insect pests. Inhibiting their activities by the use of drug-like small chemical molecules is thought to be an efficient strategy in pesticide design and development. On the basis of the crystal structure of Of ChtI, a chitinase indispensable for the molting of the insect pest Ostrinia furnacalis (Asian corn borer), here we report a chemical fragment and five variant compounds as inhibitors of Of ChtI obtained from a library of over 200 000 chemicals by a structure-based-virtual-screening approach. The compounds were synthesized with high atom economy and tested for their. Of ChtI-inhibitory activities in a bioassay. Compound 3 showed preferential inhibitory activity with a K-i value of 1.5 mu M against Of ChtI. Analysis of the structure-activity relationships of the compounds provided insight into their interactions with the enzyme active site, which may inform future work in improving the potencies of their inhibitory activities.