Design, Synthesis, and Biological Investigations of Novel Carbamoylguanidinyl Nitrobenzoxadiazoles against Chitinolytic Enzymes

Chitinase has been identified as an important target for insecticides. In this study, a series of novel chitinase inhibitors was designed and synthesized with nitrobenzoxadiazoles. Compound 8d, which contains the N-methylcarbamoylguanidinyl, exhibited high enzyme inhibitory activity and achieved nanomolar inhibition against OfChtI (IC50 = 12.3 nM). Delightfully, it was also found to possess significant inhibitory activity against OfHex1 (IC50 = 1.76 μM). The computational simulation results indicated that compound 8d interacted with OfChtI and OfHex1 in similar modes through hydrogen bonds and hydrophobic and π–π interactions. Insecticidal activity studies revealed that compound 8d showed high mortality against the Lepidoptera Plutella xylostella (mortality rate = 81%) at 200 mg/L. Toxicity studies indicated that compound 8d exhibited negligible toxicity to the natural enemy Trichogramma ostriniae. These results indicate that compound 8d may be a promising candidate for the development of environmentally friendly chitinase inhibitors. Moreover, this study provides a new angle for the design of innovative inhibitors of chitinolytic enzymes.