Virtual screening

Bioassay

Pesticide

Larva

Chemical structure

Organic chemistry

Enzyme

Chemistry

Ecology

Structure–activity relationship

In vitro

Ostrinia furnacalis

Lead compound

Chitinase

Active site

Moulting

Biochemistry

Botany

Computational biology

Stereochemistry

Drug discovery

Biology

Journal of Agricultural and Food Chemistry

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 OfChtI, 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 OfChtI 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 OfChtI-inhibitory activities in a bioassay. Compound 3 showed preferential inhibitory activity with a Ki value of 1.5 μΜ against OfChtI. 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.

Structure-Based Virtual Screening, Compound Synthesis, and Bioassay for the Design of Chitinase Inhibitors