A Potential Multitarget Insect Growth Regulator Candidate: Design, Synthesis, and Biological Activity of Novel Acetamido Derivatives Containing Hexacyclic Pyrazole Carboxamides.

Insect growth regulators (IGRs) are important green insecticides that disrupt normal growth and development in insects to reduce the harm caused by pests to crops. The ecdysone receptor (EcR) and three chitinases ChtI, ChtII, and Chi-h are closely associated with the molting stage of insects. Thus, they are considered promising targets for the development of novel insecticides such as IGRs. Our previous work identified a dual-target compound , which could act simultaneously on both EcR and ChtI. In the present study, was first found to have inhibitory activities against ChtII and Chi-h, too. Subsequently, taking as a lead compound, 19 novel acetamido derivatives were rationally designed and synthesized by introducing an acetamido moiety into the amide bridge based on the flexibility of the binding cavities of with EcR and three chitinases. Then, their insecticidal activities against (), (), and () were carried out. The bioassay results revealed that most of these acetamido derivatives possessed moderate to good larvicidal activities against three lepidopteran pests. Especially, compound displayed excellent insecticidal activities against (LC, 93.32 mg/L), (LC, 114.79 mg/L), and (86.1% mortality at 500 mg/L), significantly better than that of . In addition, further protein validation and molecular docking demonstrated that could act simultaneously on EcR (17.7% binding activity at 8 mg/L), ChtI (69.2% inhibitory rate at 50 μM), ChtII (71.5% inhibitory rate at 50 μM), and Chi-h (73.9% inhibitory rate at 50 μM), indicating that is a potential lead candidate for novel multitarget IGRs. This work provides a promising starting point for the development of novel types of IGRs as pest management agents.