Discovery of Potent N-Methylcarbamoylguanidino Insect Growth Regulators Targeting OfChtI and OfChi-h

Insect growth regulators (IGRs) are important insecticides that reduce the harm caused by insects to crops by controlling pest population growth. Chitinases are closely associated with insect growth and are among the most important glycoside hydrolases. Thus, Chitinase is an attractive target for the development of novel insecticides. In this study, we designed and synthesized a series of novel and highly potent insecticides targeting OfChtI and OfChi-h in insects. Enzymatic activity tests showed that most compounds exhibited a potent inhibitory activity against OfCh-h. Binding mode analysis revealed that the target compounds bound to the -1 active subsite of Chitinase through the key pharmacophore N-methylcarbamoylguanidino. Compounds 6e, 6g, 6j, and 6o significantly affected the growth and development of Plutella xylostella at 200 mg/L. Our study provides novel insights for the development of potent insecticide-targeted Chitinase combinations based on receptors and ligands.