Abstract：
BACKGROUND: Sheath blight and bakanae disease, prominent among emerging rice ailments, exert a profound impact on rice productivity, causing severe impediments to crop yield. Excessive use of older fungicides may lead to the development of resistance in the pathogen. Indeed, a pressing and immediate need exists for novel, low-toxicity and highly selective fungicides that can effectively combat resistant fungal strains.
RESULTS: A series of 20 isoxazole derivatives were synthesized using alkoxy/halo acetophenones and N,N-dimethylformamidedimethylacetal. These compounds were characterized by various spectroscopic techniques, namely 1H nuclear magnetic resonance (NMR), 13C NMR and liquid chromatography-high-resolution mass spectrometry, and were evaluated for their fungicidal activity against Rhizoctonia solani and Fusarium fujikuroi. Compound 5n (5-(2-chlorophenyl) isoxazole) exhibited highest activity (effective dose for 50% inhibition [ED50] = 4.43 μg mL-1) against R. solani, while 5p (5-(2,4-dichloro-2-hydroxylphenyl) isoxazole) exhibited highest activity (ED50 = 6.7 μg mL-1) against F. fujikuroi. Two-dimensional quantitative structural-activity relationship (QSAR) analysis, particularly multiple linear regression (MLR) (Model 1), highlighted chi6chain and DistTopo as the key descriptors influencing fungicidal activity. Molecular docking studies revealed the potential of these isoxazole derivatives as novel fungicides targeting sterol 14α-demethylase enzyme, suggesting their importance as crucial intermediates for the development of novel and effective fungicides.
CONCLUSIONS: All test compounds were effective in inhibiting both fungi, according to the QSAR model, with various descriptors, such as structural, molecular shape analysis, electronic and thermodynamic, playing an important role. Molecular docking studies confirmed that these compounds can potentially replace commercially available fungicides and help control fungal pathogens in rice crops effectively. © 2024 Society of Chemical Industry.
RESULTS: A series of 20 isoxazole derivatives were synthesized using alkoxy/halo acetophenones and N,N-dimethylformamidedimethylacetal. These compounds were characterized by various spectroscopic techniques, namely 1H nuclear magnetic resonance (NMR), 13C NMR and liquid chromatography-high-resolution mass spectrometry, and were evaluated for their fungicidal activity against Rhizoctonia solani and Fusarium fujikuroi. Compound 5n (5-(2-chlorophenyl) isoxazole) exhibited highest activity (effective dose for 50% inhibition [ED50] = 4.43 μg mL-1) against R. solani, while 5p (5-(2,4-dichloro-2-hydroxylphenyl) isoxazole) exhibited highest activity (ED50 = 6.7 μg mL-1) against F. fujikuroi. Two-dimensional quantitative structural-activity relationship (QSAR) analysis, particularly multiple linear regression (MLR) (Model 1), highlighted chi6chain and DistTopo as the key descriptors influencing fungicidal activity. Molecular docking studies revealed the potential of these isoxazole derivatives as novel fungicides targeting sterol 14α-demethylase enzyme, suggesting their importance as crucial intermediates for the development of novel and effective fungicides.
CONCLUSIONS: All test compounds were effective in inhibiting both fungi, according to the QSAR model, with various descriptors, such as structural, molecular shape analysis, electronic and thermodynamic, playing an important role. Molecular docking studies confirmed that these compounds can potentially replace commercially available fungicides and help control fungal pathogens in rice crops effectively. © 2024 Society of Chemical Industry.
摘要：
背景：纹枯病和bakanae病，在新兴的水稻疾病中突出，对水稻生产力产生深远的影响，对作物产量造成严重阻碍。过量使用较旧的杀真菌剂可能导致病原体产生抗性。的确,迫切需要小说，能有效对抗耐药真菌菌株的低毒和高选择性杀菌剂结果:利用烷氧基/卤代苯乙酮和N,N-二甲基甲酰胺二甲基缩醛。这些化合物通过各种光谱技术表征。1HNMR,13CNMR和LC-HRMS，并评估了它们对solani根瘤菌和Fujikuroi镰刀菌的杀真菌活性。化合物5n（5-（2-氯苯基）异恶唑）对R.solani表现出最高的活性（ED50=4.43μgmL-1），而5p（5-（2,4-二氯-2-羟基苯基）异恶唑）对F.fujikuroi表现出最高的活性（ED50=6.7μgmL-1）。2D-定量结构活性关系(2D-QSAR)分析,特别是MLR(模型1)，强调chi6链和DistTopo是影响杀真菌活性的关键描述符。分子对接研究揭示了这些异恶唑衍生物作为靶向固醇14α-脱甲基酶的新型杀菌剂的潜力，表明它们作为开发新型有效杀菌剂的关键中间体的重要性。
结论：所有受试化合物均有效抑制两种真菌，根据QSAR模型，各种描述符，如结构，分子形状分析，电子,和热力学起着重要的作用。分子对接研究证实，这些化合物可以替代市售的杀菌剂，并有助于有效控制水稻作物中的真菌病原体。本文受版权保护。保留所有权利。
结论：所有受试化合物均有效抑制两种真菌，根据QSAR模型，各种描述符，如结构，分子形状分析，电子,和热力学起着重要的作用。分子对接研究证实，这些化合物可以替代市售的杀菌剂，并有助于有效控制水稻作物中的真菌病原体。本文受版权保护。保留所有权利。
