Rational Design of N-Methylcarbamoylguanidinyl Derivatives as Highly Potent Dual-Target Chitin Hydrolase Inhibitors for Retarding Growth of Pest Insects

Chitin degradation is a vital process for the growth of insects. Chitin hydrolase OfChtI and β-N-acetylhexosaminidase OfHex1 are two key enzymes involved in hydrolyzing the chitin of insects' cuticles. Thus, they are considered promising targets for preventing and controlling agricultural pests. In this study, we designed and synthesized a series of compounds bearing N-methylcarbamoylguanidinyl and N-methoxycarbonylguanidinyl as dual-target inhibitors of OfChtI and OfHex1. The most potent dual-target inhibitor, compound 10d, exhibited half-maximal inhibitory concentration (IC50) values of 27.1 and 249.1 nM against OfChtI and OfHex1, respectively. Furthermore, the insecticidal activity studies showed that compounds 10a-c, 10k, and 10l bear significant effects on the growth and development of Plutella xylostella. This work provides a promising method for the development of novel chitin hydrolase inhibitors as potential pest control and management agents.