Discovery of new N-Phenylamide Isoxazoline derivatives with high insecticidal activity and reduced honeybee toxicity.

Isoxazoline is a novel structure with strong potential for controlling agricultural insect pests, but its high toxicity to honeybees limits its development in agriculture. Herein, a series of N-phenylamide isoxazoline derivatives with low honeybee toxicity were designed and synthesized using the intermediate derivatization method. Bioassay results showed that these compounds exhibited good insecticidal activity. Compounds 3b and 3f showed significant insecticidal effects against Plutella xylostella (P. xylostella) with median lethal concentrations (LC50) of 0.06 and 0.07 mg/L, respectively, comparable to that of fluralaner (LC50 = 0.02 mg/L) and exceeding that of commercial insecticide fluxametamide (LC50 = 0.52 mg/L). It is noteworthy that the acute honeybee toxicities of compounds 3b and 3f (LD50 = 1.43 and 1.63 µg/adult, respectively) were significantly reduced to 1/10 of that of fluralaner (LD50 = 0.14 µg/adult), and were adequate or lower than that of fluxametamide (LD50 = 1.14 µg/adult). Theoretical simulation using molecular docking indicates that compound 3b has similar binding modes with fluralaner and a similar optimal docking pose with fluxametamide when binding to the GABA receptor, which may contribute to its potent insecticidal activity and relatively low toxicity to honey bees. This study provides compounds 3b and 3f as potential new insecticide candidates and provides insights into the development of new isoxazoline insecticides exhibiting both high efficacy and environmental safety.

Preparation and Characterization of Insecticide/Calix[4]arene Complexes and Their Enhanced Insecticidal Activities against Plutella xylostella.

Applications of supramolecular materials in plant protection have attracted significant interest in recent years. To develop a feasible method to improve the efficacy and reduce the usage of chemical pesticides, the effect of calix[4]arene (C4A) inclusion on enhancing the insecticidal activity of commercial insecticides was investigated. Results showed that all three tested insecticides (chlorfenapyr, indoxacarb, and abamectin) with distinct molecular sizes and modes of action were able to form stable 1:1 host-guest complexes with C4A through simple preparation steps. The insecticidal activities of the complexes against Plutella xylostella were effectively enhanced compared to the guest molecule, with the synergism ratio being up to 3.05 (for indoxacarb). An obvious correlation was found between the enhanced insecticidal activity and the high binding affinity between insecticide and C4A, while the improvement in water solubility may not be a determining factor. The work would provide hints for the further development of functional supramolecular hosts as synergists in pesticide formulations.

Dehydrozingerone Inspired Discovery of Potential Broad-Spectrum Fungicidal Agents as Ergosterol Biosynthesis Inhibitors.

A series of dehydrozingerone derivatives were synthesized, and their fungicidal activities and action mechanism against Colletotrichum musae were evaluated. The bioassay result showed that most compounds exhibited excellent fungicidal activity in vitro at 50 µg mL-1. Compounds 13, 16, 18, 19, and 27 exhibited broad-spectrum fungicidal activity; especially, compounds 19 and 27 were found to have more potent fungicidal activity than azoxystrobin. The EC50 values of compounds 19 and 27 against Rhizoctonia solani were 0.943 and 0.161 µg mL-1 respectively. Moreover, compound 27 exhibited significant in vitro bactericidal activity against Xanthomonas oryzae pv. oryzae, with an EC50 value of 11.386 µg mL-1, and its curative effect (49.64%) and protection effect (51.74%) on rice bacterial blight disease was equivalent to that of zhongshengmycin (42.90%, 40.80% respectively). Compound 27 could also effectively control gray mold (87.10%, 200 µg mL-1) and rice sheath blight (100%, 200 µg mL-1; 82.89%, 100 µg mL-1) in vivo. Preliminary action mechanism study showed that compound 27 mainly acted on the cell membrane and significantly inhibited ergosterol biosynthesis in Colletotrichum musae.

Investigation of Novel Pesticides with Insecticidal and Antifungal Activities: Design, Synthesis and SAR Studies of Benzoylpyrimidinylurea Derivatives.

In order to find pesticides with insecticidal and antifungal activities, a series of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All target compounds were identified by ¹H-NMR spectroscopy and HRMS. Insecticidal and antifungal activity of these compounds were evaluated and the structure-activity relationships (SAR) were clearly and comprehensively illustrated. Compound 7, with low toxicity to zebrafish (LC50 = 378.387 µg mL-1) showed 100% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg mL-1. Both compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 13 phytopathogenic fungi), which were better than those of the commercial pesticide pyrimethanil (>50% inhibitory activities against eight phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L. during in vivo experiments.

Natural Product-Based Pesticide Discovery: Design, Synthesis and Bioactivity Studies of N-Amino-Maleimide Derivatives.

Natural products are an important source of pesticide discovery. A series of N-amino-maleimide derivatives containing hydrazone group were designed and synthesized based on the structure of linderone and methyllinderone which were isolated from Lindera erythrocarpa Makino. According to the bioassay results, compounds 2 and 3 showed 60% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg·mL−1. Furthermore, the results of antifungal tests indicated that most compounds exhibited much better antifungal activities against fourteen phytopathogenic fungi than linderone and methyllinderone and some compounds exhibited better antifungal activities than commercial fungicides (carbendazim and chlorothalonil) at 50 µg·mL−1. In particular, compound 12 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 11 phytopathogenic fungi) and compounds 12 and 14 displayed 60.6% and 47.9% inhibitory activity against Rhizoctonia cerealis at 12.5 µg·mL−1 respectively. Furthermore, compound 17 was synthesized, which lacks N-substituent at maleimide and its poor antifungal activity against Sclerotinia sclerotiorum and Rhizoctonia cerealis at 50 µg·mL−1 showed that the backbone structure of N-amino-maleimide derivatives containing hydrazone group was important to the antifungal activity.