A series of novel 1,3-benzodioxole-pyrimidine derivatives were designed and synthesized. The in vitro bioassay indicated that compounds 4e, 4g, 4n, 5c, and 5e displayed excellent fungicidal activities against test fungal strains. Especially, in the in vitro experiments, 5c exhibited a broad spectrum of fungicidal activity against Botrytis cinerea, Rhizoctonia solani, Fusarium oxysporum, Alternaria solani, and Gibberella zeae with EC50 values of 0.44, 6.96, 6.99, 0.07, and 0.57 mg/L, respectively, which were significantly more potent than those of positive control boscalid (EC50: 5.02, >50, >50, 0.16, and 1.28 mg/L). In vivo testing on tomato fruits and leaves showed that 5c displayed considerable protective and curative efficacy against A. solani. Scanning electron microscopy analysis indicated that 5c possessed a strong ability to destroy the surface morphology of mycelia and seriously interfere with the growth of the fungal pathogen. In the in vitro enzyme inhibition assay, 5c exhibited pronounced succinate dehydrogenase (SDH) inhibitory activity with an IC50 value of 3.41 μM, equivalent to that of boscalid (IC50: 3.40 μM). In addition, fluorescence quenching experiment further confirmed the strong interaction of 5c with SDH. Through chiral resolution, 5c was separated into two enantiomers. Among them, (S)-5c exhibited stronger fungicidal activity (EC50: 0.06 mg/L) and SDH inhibitory (2.92 μM) activity than the R-enantiomer (EC50: 0.17 mg/L and SDH IC50: 3.68 μM), which was in accordance with the molecular docking study (CDOCKER Interaction Energy for (R)-5c and (S)-5c: −28.23 and −29.98 kcal/mol, respectively). These results presented a promising lead for the discovery of novel SDHIs as antifungal pesticides.
To discover novel fungicidal agrochemicals for treating wheat scab, 39 novel camphor sulfonohydrazide/sulfonamide derivatives 4a−4t and 6a−6s were designed and synthesized. In the in vitro antifungal/antioomycete assay, compounds 4g, 4n, and 4o displayed significant inhibitory activities against Fusarium graminearum, Botryosphaeria dothidea, and Phytophthora capsici. Among them, 4n exhibited the best antifungal activity against F. graminearum with an EC 50 value of 0.41 mg/L, which was at the same level as that of pydiflumetofen. The in vivo experiment revealed that 4n presented excellent protective and curative efficacy toward F. graminearum. In the antifungal mechanism study, 4n could increase the cell membrane permeability and reduce the exopolysaccharide and ergosterol content of F. graminearum. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses revealed that 4n could significantly damage the surface morphology and the cell ultrastructure of mycelia to interfere with the growth of F. graminearum. Furthermore, 4n exhibited potent succinate dehydrogenase (SDH) inhibitory activity in vitro with an IC 50 value of 3.94 μM, which was equipotent to pydiflumetofen (IC 50 = 4.07 μM). The molecular dynamics simulation and docking study suggested that compound 4n could well occupy the active site and form strong interactions with the key residues of SDH. The above-mentioned results demonstrated that the title camphor sulfonohydrazide/sulfonamide derivatives could be promising lead compounds for further succinate dehydrogenase inhibitor (SDHI) fungicide development.
BACKGROUND To explore further potential natural product‐based antifungal agents, a series of novel nopol‐based carboxamide and hydrazide derivatives containing a natural pinene structure were designed, synthesized, and evaluated for their inhibitory activities against seven phytopathogenic fungi and oomycetes. RESULTS The bioassay results indicated that some compounds exhibited good inhibitory activities against Gibberella zeae, Sclerotinia sclerotiorum, and Phytophthora capsici. Among them, compound 3h displayed excellent in vitro activities against G. zeae, with EC50 values of 1.09 mg L−1, which was comparable with the commercial fungicides bixafen and carbendazim (median effective concentration [EC50] = 1.21 and 0.89 mg L−1, respectively). Notably, in vivo bioassay results suggested that compound 3h also showed prominent protective and curative effects (95.6% and 94.2%) at 200 mg L−1 against G. zeae. The scanning electron microscopy study indicated that compound 3h could destroy the morphological integrity of G. zeae hyphae. The in vitro enzyme inhibitory bioassay revealed that compound 3h exhibited potent inhibitory activity against laccase with median inhibitory concentration (IC50) values of 4.93 μm, superior to positive control cysteine (IC50 = 35.50 μm), and its binding modes with laccase were elucidated by molecular docking study. In addition, the fluorescent imaging of the dansylamide‐labeled derivatives 8 on wheat leaf epidermal cells and the hyphae of G. zeae revealed that this class of hydrazide derivatives could readily permeate into wheat leaves and reached the laccase target in fungal cells. CONCLUSION Some nopol‐based hydrazide derivatives exhibited excellent anti‐G. zeae activity and laccase inhibitory activity, which merits further development as a new fungicide candidate for controlling Fusarium head blight. © 2023 Society of Chemical Industry.
In order to find novel potential antifungal agrochemicals, a series of new 4-(1,2,4-oxadiazol-3-yl)-N-(4phenoxyphenyl)benzamide derivatives 3a-j were designed, synthesized and characterized by their 1 H-, 13 C-NMR and HRMS spectra. The preliminary antifungal assay in vitro revealed that compounds 3a-j exhibited moderate to good antifungal activity against five plant pathogenic fungi. Especially, compound 3e presented significant antifungal activity against Alternaria solani, Botrytis cinerea and Sclerotinia sclerotiorum, superior to positive control boscalid. In the in vivo antifungal assay on tomato plants and cucumber leaves, compound 3e presented good inhibition rate against B. cinerea at 200 mg/L. Molecular dynamics simulation revealed that compound 3e could bind with the active site of class II histone deacetylase (HDAC).
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