Diversity of pesticide discovery provided a solution to resistance. Here, we presented a strategy of azo-incorporating to promote the diverse developments of fungicide. A series of novel fungicides were synthesized by incorporating azobenzene derivatives into fluxapyroxad. Much better in vitro fungicidal activity increases for compound 9d were observed compared to the positive control, fluxapyroxad against Botrytis cinerea and Rhizoctonia solani. Compound 9d (IC50 = 0.03 μM) also had a great enzyme-inhibiting activity increase toward succinate dehydrogenase in comparison with fluxapyroxad (IC50 = 4.40 μM). A comparatively equivalent biological activity was observed between compounds 8a and 9d. SEM analysis helped us to observe clearly the morphology of the fungi before and after active ingredient delivery. Our results of molecular docking analysis, fluorescence quenching analysis, and enzymatic assays demonstrated that compound 8a and 9d act on SDH. An increase in inhibitory activity could be occurring after incorporation of azobenzene, which provided a new strategy for molecular design in pesticide discovery.

Succinate dehydrogenase (SDH) is one of the most important molecular targets for the development of new fungicides. Carboxamide fungicides are a class of SDH inhibitors widely used to inhibit highly destructive plant pathogens. Although cases of resistance have been found in fungal pathogens due to the unrestricted use in recent years, there is still demand for new compounds with improved fungicidal activity. Therefore, a series of ester compounds were designed to investigate potential novel antifungal molecules. First, the antifungal activity of different benzyl alcohol compounds (A1–A21) was tested, and a highly active fragment (3,5-dichlorobenzyl alcohol) was found. Subsequently, various compounds were synthesized by esterification between different acids and 3,5-dichlorobenzyl alcohol, among which compound 5 exhibited remarkable antifungal activity against Botrytis cinerea and Rhizoctonia solani with EC50 values of 6.60 and 1.61 mg/L, respectively, which were comparable to those of commercial fungicide boscalid (EC50 = 1.24 and 1.01 mg/L). In vivo testing further demonstrated that compound 5 was effective in suppressing B. cinerea (200 mg/L, 50.9%). Moreover, SDH inhibition assays, fluorescence quenching analysis, and determination of mitochondrial membrane potential revealed that compound 5 has similar effects to boscalid. Furthermore, the fungicidal activity of target compounds can be maintained by modifying the amide bond to an ester bond. These results will provide basis for the development of novel fungicides.

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Diverse molecular fragments have generally facilitated the development of drug discovery. Heterocyclic moieties could be found in most active ingredients, especially in chemical pesticides. Based on our previously reported 3,3,3‐Benzyl trifluoropropionate compounds which are of excellent insecticidal and fungicidal activity, we designed and synthesized 13 Heterocyclic Methyl Ester (HME) compounds, HME01‐HME13, comprising heterocyclic parts. Four insect species and four plant pathogens were employed in biological activities. The bioactivity assay results showed that compound HME12 exhibited certain insecticidal activity and fungicidal activity. The structure–activity relationship was preliminarily evaluated and further analyzed by density functional theory. The results might be meaningful for directing the development of such esters. Moreover, compound HME12 could be continuously studied as a precursor.

The compounds featuring α-difluorothiomethylated ketone skeleton derivatives are of particular interest in pharmaceuticals and agrochemicals. Herein, we designed novel electrophilic N-difluoromethylthiophthalimide reagents that can be easily prepared with commercially available and economical chemicals. These reagents could smoothly react with various nucleophiles, such as Grignard reagents, boronic acids, β-keto esters, and anilines, which affords structurally diverse α-difluoromethylthiolated ketones in good to excellent yields. The formal synthesis of active antifungal compounds positively confirmed the practicability of these reagents.