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 mu M). The computational simulation results indicated that compound 8d interacted with OfChtI and OfHex1 in similar modes through hydrogen bonds and hydrophobic and pi-pi 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.