Design, Synthesis, and Fungicidal Evaluation of Novel 1,3-Benzodioxole-Pyrimidine Derivatives as Potential Succinate Dehydrogenase Inhibitors

Abstract

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.

Discovery of Aryloxy-, Arylthio-, and Arylamino-Containing Acethydrazides as Fungicidal Agents

“…Food supply is related to global security and stability, while world grain output has declined due to various superimposed factors in 2022. Therein, phytopathogenic fungi, such as the troublesome filamentous fungi Fusarium graminearum, Rhizoctonia solani, and Pyricularia grisea, seriously affect grain yield and quality. − The application of fungicides is the most common method of controlling plant diseases and is essential to improve and secure food production. , In China, Shouguang and Shenxian are the two largest producing cities for facility vegetables. However, with the long-term use of traditional fungicides, the resistance of plant pathogens such as Botrytis cinerea and Colletotrichum gloeosporioides in facility vegetables has become more serious.…”

“…1−3 The application of fungicides is the most common method of controlling plant diseases and is essential to improve and secure food production. 4,5 In China, Shouguang and Shenxian are the two largest producing cities for facility vegetables. However, with the long-term use of traditional fungicides, the resistance of plant pathogens such as Botrytis cinerea and Colletotrichum gloeosporioides in facility vegetables has become more serious.…”

Virtual Screening and Quantitative Structure–Activity Relationship of Moringa oleifera with Melanoma Antigen A (MAGE-A) Genes against the Therapeutics of Non-Small Cell Lung Cancers (NSCLCs)

“…1,3-Benzodioxole has been reported to have a strong antioxidative capacity [ 50 ]. 1,3-Benzodioxole-pyrimidine and its derivatives have been identified as potential succinate dehydrogenase inhibitors and as antifungal agents [ 51 ]. The same compound has also been reported to have anticancer properties in both in vitro and in vivo studies against breast, liver, bone, and lung cancers [ 52 ].…”

Design, Synthesis, and Biological Evaluation of Novel Pyrazol-5-yl-benzamide Derivatives Containing Oxazole Group as Potential Succinate Dehydrogenase Inhibitors

“…sclerotiorum were inoculated on a PDA medium containing compound C13 (concentration = 0.69 mg/L) and compound C14 (concentration = 0.26 mg/L) and cultured at 25 °C for 48 h. The detailed treatment procedure of S. sclerotiorum hyphae for SEM observation was as previously described . Supporting Information describes the exact experimental method.…”