Discovery of Azo-Aminopyrimidines as Novel and Potent Chitinase Of Chi-h Inhibitors via Structure-Based Virtual Screening and Rational Lead Optimization

Chitinase Of Chi-h, from the destructive agricultural pest Ostrinia furnacalis, is considered as a promising target for green pest control and management. In this study, structure-based virtual screening and rational molecular optimization led to the synthesis of a series of azo-aminopyrimidine derivatives as a novel class of Of Chi-h inhibitors. Among them, the most potent compound 8f, with a benzyl on the amino group at the 4-position of pyrimidine, exhibited a K-i value of 64.7 nM against Of Chi-h. In addition, molecular docking studies were carried out to investigate the basis for the potency of the aminopyrimidines against Of Chi h. Furthermore, the insecticidal activity of the target compounds against Plutella xylostella and Ostrinia nubilalis was assessed, and the potent Of Chi-h inhibitors 8f and 8i showed higher insecticidal activity than the control pesticide hexaflumuron. The present work revealed that the azo-aminopyrimidine skeletons characterized by concise chemical structure and high efficiency could be further developed as potential pesticides for the control of lepidopteran pests.