Decade of research on insect chitinase inhibitors: insights from molecular structure to biological function

Insect chitinases are critical enzymes governing insect growth and development. Their absence in higher animals and plants positions them as prime targets for the development of selective insecticides. This review synthesizes a decade of research on GH18 family chitinase inhibitors, with a focus on their structural characteristics, inhibition mechanisms, and biological activities. Using the chitinases OfChtI, OfChtII, and OfChi-h from the Asian corn borer as case studies, we examine their TIM barrel architecture, catalytic mechanisms, and roles in molting and immune defense. Research reveals that diverse inhibitor-such as berberine, tetrahydrobenzothiophene, heptacyclic/hexacyclic. Pyrazolyl amide, bis-pyridine pyrimidine, piperine, azo-aminopyrimidine, N-methylcarbamoylguanidinyl, and lunidonine derivative-engage the enzyme's active site via competitive inhibition, π-π stacking, hydrogen bonding, and hydrophobic interactions, effectively disrupting insect growth and development. Notably, novel derivatives demonstrate potent inhibitory activity at nanomolar to micromolar concentrations, with certain compounds exhibiting insecticidal efficacy comparable to or exceeding that of commercial insecticides, while maintaining low toxicity to non-target organisms. These insights provide a robust theoretical and practical framework for designing highly effective, low-toxicity, and selective insect growth regulators, advancing sustainable agricultural practices.