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 Of ChtI (IC 50 = 12.3 nM). Delightfully, it was also found to possess significant inhibitory activity against Of Hex1 (IC 50 = 1.76 μM). The computational simulation results indicated that compound 8d interacted with Of ChtI and Of Hex1 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.