Chitinase is one of the most important glycoside hydrolyases, widely existing in bacteria, fungi, insects, and plants. It is involved in fungal cell wall remodeling and insect molting. Chitinase inhibitors are an effective means of controlling pathogens and pests. Natural product argifin is a 17-membered pentapeptide that exhibits efficient chitinase inhibitory activity. However, the complexity of the synthetic process results in a lot of restrictions for wide range of applications. In this work, we designed a series of azamacrolide chitinase inhibitors based on the structural features of argifin that have high inhibitory activities against bacterial and insectile chitinase. The most potent chitinase inhibitor compound 19c exhibited IC 50 values of 56 nM and 110 nM against Of Chi-h and SmChiB, respectively. The molecular docking and molecular dynamics simulations revealed that all inhibitors were bound to the −1 subsite of chitinases via N-methylcarbamoylguanidinyl as well as argifin. Finally, a bioactivity assay against pests was carried out. Compound 18a showed 80% mortality for Mythimna separata at a concentration of 50 mg/L. Besides, insecticides 19b and 19c exhibited high mortality against Plutella xylostella (76 and 73% mortalities at 50 mg/L, respectively).

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In an effort to develop novel molecules with suitable insecticidal activities, 23,24-alkene-avermectin B2a derivatives have been synthesized via a one-pot multistep reaction using avermectin B2a, a byproduct of avermectin fermentation, as a starting material. All products and intermediates were characterized by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry. Bioassay results showed that the LC 50 values of compounds 4 and 9 against Meloidogyne incognita were 0.63 and 0.50 mg/L, respectively, similar to that of avermectin (0.46 mg/L). Importantly, the LC 50 values of compound 9 against Tetranychus cinnabarinus and Mythimna separate were 0.0067 and 0.047 mg/L, respectively, superior to that of avermectin. Through field experiments, it could be found that spraying 0.25% water-dispersible granules of compound 9 345 g ha −1 could effectively control M. incognita outbreaks, with an efficacy of 84.9%. Combined with toxicity experiments, it could be further inferred that compound 9 may be useful as a lowtoxicity pesticide. In summary, we efficiently synthesized a new B2a derivative as a potential pesticide and offered an important way for improving the utilization efficiency of avermectin fermentation products. In doing so, the environmental pollution associated with fermentation byproducts may be greatly reduced, potentially enabling a sustainable avermectin fermentation process.

To discover new nematicidal succinate dehydrogenase (SDH) inhibitors with novel structures, we conducted a virtual screening of the ChemBridge library with 1.7 million compounds based on ligand‐pocket interactions. The homology model of Caenorhabditis elegans SDH was established, along with a pharmacophore model based on ligand‐pocket interactions. After the pharmacophore‐based and docking‐based screening, 19 compounds were selected for the subsequent enzymatic assays. The results showed that compound 1 (ID: 7607321) exhibited inhibitory activity against SDH with a determined IC50 value of 19.6 μM. Structural modifications and nematicidal activity studies were then carried out, which provided further evidence that compound 1 exhibited excellent nematicidal activity. Molecular dynamics simulations were then conducted to investigate the underlying molecular basis for the potency of these inhibitors against SDH. This work provides a reliable strategy and useful information for the future design of nematode SDH inhibitors.