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

Abstract

Chitinase OfChi-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 OfChi-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 OfChi-h. In addition, molecular docking studies were carried out to investigate the basis for the potency of the aminopyrimidines against OfChi-h. Furthermore, the insecticidal activity of the target compounds against Plutella xylostella and Ostrinia nubilalis was assessed, and the potent OfChi-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.

Keywords: OfChi-h; aminopyrimidine derivatives; chitinase; inhibitor; insecticidal activity; virtual screening.