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1.
Sci Rep ; 14(1): 12700, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830957

RESUMO

Fungicide mixtures are an effective strategy in delaying the development of fungicide resistance. In this research, a fixed ratio ray design method was used to generate fifty binary mixtures of five fungicides with diverse modes of action. The interaction of these mixtures was then analyzed using CA and IA models. QSAR modeling was conducted to assess their fungicidal activity through multiple linear regression (MLR), support vector machine (SVM), and artificial neural network (ANN). Most mixtures exhibited additive interaction, with the CA model proving more accurate than the IA model in predicting fungicidal activity. The MLR model showed a good linear correlation between selected theoretical descriptors by the genetic algorithm and fungicidal activity. However, both ML-based models demonstrated better predictive performance than the MLR model. The ANN model showed slightly better predictability than the SVM model, with R2 and R2cv at 0.91 and 0.81, respectively. For external validation, the R2test value was 0.845. In contrast, the SVM model had values of 0.91, 0.78, and 0.77 for the same metrics. In conclusion, the proposed ML-based model can be a valuable tool for developing potent fungicidal mixtures to delay fungicidal resistance emergence.


Assuntos
Fungicidas Industriais , Aprendizado de Máquina , Relação Quantitativa Estrutura-Atividade , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Máquina de Vetores de Suporte , Redes Neurais de Computação , Modelos Lineares
2.
Pestic Biochem Physiol ; 202: 105900, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879291

RESUMO

The phytopathogenic oomycete Phytophthora litchii is the culprit behind the devastating disease known as "litchi downy blight", which causes large losses in litchi production. Although fluopimomide exhibits strong inhibitory efficacy against P. litchii, the exact mechanism of resistance is still unknown. The sensitivity of 137 P. litchii isolates to fluopimomide was assessed, and it was discovered that the median effective concentration (EC50) of the fungicide had a unimodal frequency distribution with a mean value of 0.763 ± 0.922 µg/mL. Comparing the resistant mutants to the equivalent parental isolates, the resistance mutants' survival fitness was much lower. While there was no cross-resistance between fluopimomide and other oomycete inhibitors, there is a notable positive cross-resistance between fluopimomide and fluopicolide. According to the thorough investigation, P. litchii had a moderate chance of developing fluopimomide resistance. The point mutations N771S and K847N in the VHA-a of P. litchii (PlVHA-a) were present in the fluopimomide-resistant mutants, and the two point mutations in PlVHA-a conferring fluopimomide resistance were verified by site-directed mutagenesis in the sensitive P. capsici isolate BYA5 and molecular docking.


Assuntos
Fungicidas Industriais , Phytophthora , Mutação Puntual , Phytophthora/efeitos dos fármacos , Phytophthora/genética , Fungicidas Industriais/farmacologia , Morfolinas/farmacologia , Benzamidas , Piridinas
3.
Pestic Biochem Physiol ; 202: 105949, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879335

RESUMO

Quinone outside inhibitor (QoI) has been applied to manage taro leaf blight caused by Phytophthora colocasiae in southeastern of China for many years. The risk of P. colocasiae to QoI and the potential resistant mechanism remain unknown. In this study, the 74 P. colocasiae strains were sampled from southeastern of China. Sequence analysis of the QoI target Cytb showed one nucleotide variant in the fragment of this gene in this population, producing two haplotypes. The nucleotide variant leads to codon change at 142 (GGT to GCT) producing A142 (alanine) and G142 (glycine) in Hap_1 and Hap_2 strains, respectively. The sensitivity differentiation to azoxystrobin of two haplotypes were observed in vitro. The Hap_1 and Hap_2 strains were confirmed resistant and sensitive by control efficacy of label rate fungicide application, which was 3.0% and 88.8% treated with 500 µg/mL azoxystrobin, respectively. In addition, 10.0 µg/mL azoxystrobin plus 50 µg/mL salicylhydroxamic acid (SHAM) supplemented in PDA medium was identified as a discriminatory dose for differentiation of these two phenotype strains. The azoxystrobin resistant frequency reached 86.5%, indicating prevalence of QoI resistance in the field. Further fitness related features showed that no significant difference in temperature sensitivity, mycelial growth rate, sporangia production, zoospore release and aggressiveness between azoxystrobin-resistant and sensitive strains indicating no potential fitness cost for azoxystrobin resistance. Taken together, azoxystrobin resistance need to be taken into consideration to manage taro leaf blight in southeastern of China.


Assuntos
Fungicidas Industriais , Phytophthora , Pirimidinas , Estrobilurinas , Estrobilurinas/farmacologia , Fungicidas Industriais/farmacologia , China , Phytophthora/efeitos dos fármacos , Phytophthora/genética , Pirimidinas/farmacologia , Doenças das Plantas/microbiologia , Farmacorresistência Fúngica/genética
4.
Pestic Biochem Physiol ; 202: 105973, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879316

RESUMO

Using a high-efficiency insecticide in combination with fungicides that have different mechanisms of action is a conventional method in the current management of brown planthopper (BPH) resistance. In this study, we investigate the separate and combined effects of the low-toxicity fungicide validamycin and the non-cross-resistant insecticide imidacloprid on the fitness and symbiosis of BPH. These research results indicate that when the proportion of active ingredients in validamycin is combined with imidacloprid at a ratio of 1:30, the toxicity ratio and co-toxicity coefficient are 1.34 and 691.73, respectively, suggesting that the combination has a synergistic effect on the control of BPH. The number of yeast-like symbiotic (YLS) and dominant symbiotic (Noda) in the imidacloprid + validamycin groups were significantly lower than the other three treatment groups (validamycin, imidacloprid, and water). The results of the study on population fitness show that the lifespan of the BPH population in validamycin, imidacloprid, and imidacloprid + validamycin was shortened. Notably, the BPH populations in the imidacloprid + validamycin groups were significantly lower than other groups in terms of average generation cycle, intrinsic growth rate, net reproduction rate, finite rate of increase, and fitness. The Real-time quantitative PCR showed that validamycin and imidacloprid + validamycin can significantly inhibit the expression of the farnesyl diphosphate farnesyl transferase gene (EC2.5.1.21) and uricase gene (EC1.7.3.3), with imidacloprid + validamycin demonstrating the most pronounced inhibitory effect. Our research results can provide insights and approaches for delaying resistance and integrated management of BPH.


Assuntos
Hemípteros , Inseticidas , Neonicotinoides , Nitrocompostos , Simbiose , Animais , Hemípteros/efeitos dos fármacos , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Inseticidas/farmacologia , Inositol/análogos & derivados , Inositol/farmacologia , Imidazóis/farmacologia , Fungicidas Industriais/farmacologia
5.
Pestic Biochem Physiol ; 202: 105933, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879325

RESUMO

Citrus sour rot is a common postharvest citrus disease caused by Geotrichum citri-aurantiiti, which has led to enormous economic losses, particularly during rainy seasons. In this study, we aimed to clarify the impact of berberine hydrochloride (BH), the hydrochloride form of an isoquinoline alkaloid, on the control efficiency of citrus sour rot and its antifungal mode against G. citri-aurantii. Results demonstrated that BH markedly impede the propagation of G. citri-aurantii by delaying the spores development from dormant stage into swollen and germinating stages, with the MIC and MFC value of 0.08 and 0.16 g L-1, respectively. When the artificially inoculated citrus fruit in control group were totally rotted, the disease incidence of BH-treated groups decreased by 35.00%-73.30%, which effectively delayed the disease progression and almost did not negatively affect fruit quality. SEM observation, CFW and PI staining images revealed that BH caused significant damage to both the cell membrane and cell wall of G. citri-aurantii spores, whereas only the cell membrane of the mycelium was affected. The impact of cell wall was related to the block of chitin and ß-1,3-glucan synthesis. Transcriptome results and further verification proved that 0.5 × MIC BH treatment affected the glycolysis pathway and TCA cycle mainly by inhibiting the production of acetyl-CoA and pyruvate. Subsequently, the activities of key enzymes declined, resulting in a further decrease in ATP levels, ultimately inhibiting the germination of spores. In conlusion, BH delays citrus sour rot mainly by disrupting carbohydrate and energy metabolism of G. citri-aurantii spores.


Assuntos
Berberina , Citrus , Metabolismo Energético , Geotrichum , Doenças das Plantas , Esporos Fúngicos , Citrus/microbiologia , Geotrichum/efeitos dos fármacos , Geotrichum/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Berberina/farmacologia , Metabolismo Energético/efeitos dos fármacos , Esporos Fúngicos/efeitos dos fármacos , Metabolismo dos Carboidratos/efeitos dos fármacos , Fungicidas Industriais/farmacologia
6.
Fungal Biol ; 128(4): 1847-1858, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38876537

RESUMO

Post-harvest decay of fresh agricultural produce is a major threat to food security globally. Synthetic fungicides, commonly used in practice for managing the post-harvest losses, have negative impacts on consumers' health. Studies have reported the effectiveness of fungal isolates from plants as biocontrol agents of post-harvest diseases, although this is still poorly established in tomatoes (Solanum lycopersicum L. cv. Jasmine). In this study, 800 endophytic fungi were isolated from mature green and ripe untreated and fungicide-treated tomato fruits grown in open soil and hydroponics systems. Of these, five isolates (Aureobasidium pullulans SUG4.1, Coprinellus micaceus SUG4.3, Epicoccum nigrum SGT8.6, Fusarium oxysporum HTR8.4, Preussia africana SUG3.1) showed antagonistic properties against selected post-harvest pathogens of tomatoes (Alternaria alternata, Fusarium solani, Fusarium oxysporum, Geotrichum candidum, Rhizopus stolonifera, Rhizoctonia solani), with Lactiplantibacillus plantarum as a positive control. P. africana SUG3.1 and C. micaceus SUG4.3 significantly inhibited growth of all the pathogens, with antagonistic capabilities comparable to that exhibited by L. plantarum. Furthermore, the isolates produced an array of enzymes, including among others, amylase, cellulose and protease; and were able to utilize several carbohydrates (glucose, lactose, maltose, mannitol, sucrose). In conclusion, P. africana SUG3.1 and C. micaceus SUG4.3 may complement L. plantarum as biocontrol agents against post-harvest pathogens of tomatoes.


Assuntos
Endófitos , Frutas , Fungos , Doenças das Plantas , Solanum lycopersicum , Solanum lycopersicum/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Frutas/microbiologia , Endófitos/isolamento & purificação , Endófitos/fisiologia , Endófitos/classificação , Fungos/isolamento & purificação , Fungos/fisiologia , Fungos/classificação , Fungos/efeitos dos fármacos , Antibiose , Agentes de Controle Biológico , Fungicidas Industriais/farmacologia
7.
J Agric Food Chem ; 72(22): 12415-12424, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38779960

RESUMO

A series of novel 2-Ar-1,2,3-triazole derivatives were designed and synthesized based on our previously discovered active compound 6d against Rhizoctonia solani. Most of these compounds exhibited good antifungal activity against R. solani at a concentration of 25 µg/mL. Based on the results of biological activity, we established a three-dimensional quantitative structure-activity relationship (3D-QSAR) model that guided the synthesis of compound 7y. Compound 7y exhibited superior activity against R. solani (EC50 = 0.47 µg/mL) compared to the positive controls hymexazol (EC50 = 12.80 µg/mL) and tebuconazole (EC50 = 0.87 µg/mL). Furthermore, compound 7y demonstrated better protective activity than the aforementioned two commercial fungicides in both detached leaf assays and greenhouse experiments, achieving 56.21% and 65.75% protective efficacy, respectively, at a concentration of 100 µg/mL. The ergosterol content was determined and molecular docking was performed to explore the mechanism of these active molecules. DFT calculation and MEP analysis were performed to illustrate the results of this study. These results suggest that compound 7y could serve as a novel 2-Ar-1,2,3-triazole lead compound for controlling R. solani.


Assuntos
Desenho de Fármacos , Fungicidas Industriais , Simulação de Acoplamento Molecular , Doenças das Plantas , Relação Quantitativa Estrutura-Atividade , Rhizoctonia , Triazóis , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Estrutura Molecular , Hidrazinas/química , Hidrazinas/farmacologia
8.
J Agric Food Chem ; 72(22): 12459-12468, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38771934

RESUMO

A series of 19 novel eugenol derivatives containing a 1,2,3-triazole moiety was synthesized via a two-step process, with the key step being a copper(I)-catalyzed azide-alkyne cycloaddition reaction. The compounds were assessed for their antifungal activities against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. Triazoles 2k, 2m, 2l, and 2n, at 100 ppm, were the most effective, reducing mycelial growth by 88.3, 85.5, 82.4, and 81.4%, respectively. Molecular docking calculations allowed us to elucidate the binding mode of these derivatives in the catalytic pocket of C. gloeosporioides CYP51. The best-docked compounds bind closely to the heme cofactor and within the channel access of the lanosterol (LAN) substrate, with crucial interactions involving residues Tyr102, Ile355, Met485, and Phe486. From such studies, the antifungal activity is likely attributed to the prevention of substrate LAN entry by the 1,2,3-triazole derivatives. The triazoles derived from natural eugenol represent a novel lead in the search for environmentally safe agents for controlling C. gloeosporioides.


Assuntos
Carica , Colletotrichum , Eugenol , Fungicidas Industriais , Simulação de Acoplamento Molecular , Doenças das Plantas , Triazóis , Colletotrichum/efeitos dos fármacos , Eugenol/farmacologia , Eugenol/química , Carica/química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Relação Estrutura-Atividade , Desenho de Fármacos , Proteínas Fúngicas/química , Estrutura Molecular
9.
Nat Commun ; 15(1): 4357, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821954

RESUMO

Triazoles are widely used to control pathogenic fungi. They inhibit the ergosterol biosynthetic pathway, but the precise mechanisms leading to fungicidal activities in many fungal pathogens are poorly understood. Here, we elucidate the mode of action of epoxiconazole and metconazole in the wheat pathogen Zymoseptoria tritici and the rice blast fungus Magnaporthe oryzae. We show that both azoles have fungicidal activity and reduce fluidity, but not integrity, of the plasma membrane. This impairs localisation of Cdc15-like F-BAR proteins, resulting in defective actin ring assembly and incomplete septation. However, mutant studies and pharmacological experiments in vitro and in planta show that azole lethality is due to a combination of reactive oxygen species-induced apoptosis and macroautophagy. Simultaneous inhibition of both programmed cell death pathways abolishes azole-induced cell death. Other classes of ergosterol biosynthesis inhibitors also induce apoptosis and macroautophagy, suggesting that activation of these two cell death pathways is a hallmark of ergosterol synthesis-targeting fungicides. This knowledge will inform future crop protection strategies.


Assuntos
Apoptose , Ascomicetos , Fungicidas Industriais , Doenças das Plantas , Espécies Reativas de Oxigênio , Apoptose/efeitos dos fármacos , Doenças das Plantas/microbiologia , Ascomicetos/efeitos dos fármacos , Ascomicetos/metabolismo , Ascomicetos/patogenicidade , Fungicidas Industriais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Triticum/microbiologia , Azóis/farmacologia , Ergosterol/biossíntese , Ergosterol/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Autofagia/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Oryza/microbiologia , Oryza/metabolismo , Triazóis/farmacologia , Produtos Agrícolas/microbiologia
10.
Food Chem ; 453: 139669, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38781900

RESUMO

Green mold is a common postharvest disease infected by Penicillium digitatum that causes citrus fruit decay, and severely affects fruit storage quality. This work aimed to investigate the antifungal activity of Sanxiapeptin against P. digitatum, and elucidate the possible mechanisms involved. Sanxiapeptin was capable of inhibiting spore germination, germ tube length and mycelial growth. The SYTOX green staining assay revealed that Sanxiapeptin targeted the fungal membrane, and changed the membrane permeability, leading to the leakage of cell constituents. Meanwhile, Sanxiapeptin could influence the cell wall permeability and integrity by increasing the activities of chitinase and glucanase, resulting in abnormal chitin consumption and the decrease of glucan. Intriguingly, Sanxiapeptin could effectively control postharvest decay in citrus fruits, and activate the host resistance responses by regulating the phenylpropanoid pathway. In conclusion, Sanxiapeptin exhibits multiphasic antifungal mechanisms of action to control green mold in citrus fruits, shows great potential as novel food preservatives.


Assuntos
Citrus , Conservantes de Alimentos , Frutas , Penicillium , Doenças das Plantas , Citrus/microbiologia , Citrus/química , Penicillium/crescimento & desenvolvimento , Penicillium/efeitos dos fármacos , Doenças das Plantas/microbiologia , Frutas/microbiologia , Frutas/química , Frutas/crescimento & desenvolvimento , Frutas/efeitos dos fármacos , Conservantes de Alimentos/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Conservação de Alimentos/métodos , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química
11.
Bioorg Med Chem Lett ; 108: 129813, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38788964

RESUMO

Succinate dehydrogenase inhibitors are essential fungicides used in agriculture. To explore new pyrazole-carboxamides with high fungicidal activity, a series of N-substitutedphenyl-3-di/trifluoromethyl-1-methyl-1H-pyrazole-4-carboxamides bearing a branched alkyl ether moiety were designed and synthesized. The in vitro bioassay indicated that some target compounds displayed appreciable fungicidal activity. For example, compounds 5d and 5e showed high efficacy against S. sclerotiorum with EC50 values of 3.26 and 1.52 µg/mL respectively, and also exhibited excellent efficacy against R. solani with EC50 values of 0.27 and 0.06 µg/mL respectively, which were comparable or superior to penflufen. The further in vivo bioassay on cucumber leaves demonstrated that 5e provided strong protective activity of 94.3 % against S. sclerotiorum at 100 µg/mL, comparable to penflufen (99.1 %). Cytotoxicity assessment against human renal cell lines (239A cell) revealed that 5e had low cytotoxicity within the median effective concentrations. Docking study of 5e with succinate dehydrogenase illustrated that R-5e formed one hydrogen bond and two π-π stacking interactions with amino acid residues of target enzyme, while S-5e formed only one π-π stacking interaction with amino acid residue. This study provides a valuable reference for the design of new succinate dehydrogenase inhibitor.


Assuntos
Fungicidas Industriais , Simulação de Acoplamento Molecular , Pirazóis , Succinato Desidrogenase , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Humanos , Relação Estrutura-Atividade , Fungicidas Industriais/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ascomicetos/efeitos dos fármacos , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Relação Dose-Resposta a Droga , Éteres/química , Éteres/farmacologia , Éteres/síntese química , Rhizoctonia
12.
J Agric Food Chem ; 72(22): 12373-12386, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38775264

RESUMO

Finding highly active molecular scaffold structures is always the key research content of new pesticide discovery. In the research and development of new pesticides, the discovery of new agricultural molecular scaffold structures and new targets still faces great challenges. In recent years, quinoline derivatives have developed rapidly in the discovery of new agriculturally active molecules, especially in the discovery of fungicides. The unique quinoline scaffold has many advantages in the discovery of new pesticides and can provide innovative and feasible solutions for the discovery of new pesticides. Therefore, we reviewed the use of quinoline derivatives and their analogues as molecular scaffolds in the discovery of new pesticides since 2000. We systematically summarized the agricultural biological activity of quinoline compounds and discussed the structure-activity relationship (SAR), physiological and biochemical properties, and mechanism of action of the active compounds, hoping to provide ideas and inspiration for the discovery of new pesticides.


Assuntos
Praguicidas , Quinolinas , Quinolinas/química , Praguicidas/química , Praguicidas/farmacologia , Relação Estrutura-Atividade , Descoberta de Drogas , Estrutura Molecular , Animais , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Humanos
13.
J Appl Microbiol ; 135(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38802124

RESUMO

AIMS: Anthracnose caused by Colletotrichum species is one of the most devastating diseases of fruits and crops. We isolated and identified an antifungal compound from the mushroom Coprinus comatus and investigated its inhibitory potential against anthracnose disease-causing fungi with the goal of discovering natural products that can suppress anthracnose-caused plant disease. METHODS AND RESULTS: The culture filtrate of C. comatus was subjected to a bioassay-guided isolation of antifungal compounds. The active compound was identified as orsellinaldehyde (2,4-dihydroxy-6-methylbenzaldehyde) based on mass spectroscopy and nuclear magnetic resonance analyses. Orsellinaldehyde displayed broad-spectrum inhibitory activity against different plant pathogenic fungi. Among the tested Colletotrichum species, it exhibited the lowest IC50 values on conidial germination and germ tube elongation of Colletotrichum orbiculare. The compound also showed remarkable inhibitory activity against Colletotrichum gloeosporiodes. The staining of Colletotrichum conidia with fluorescein diacetate and propidium iodide demonstrated that the compound is fungicidal. The postharvest in-vivo detached fruit assay indicated that orsellinaldehyde suppressed anthracnose lesion symptoms on mango and cucumber fruits caused by C. gloeosporioides and C. orbiculare, respectively. CONCLUSIONS: Orsellinaldehyde was identified as a potent antifungal compound from the culture filtrate of C. comatus. The inhibitory and fungicidal activities of orsellinaldehyde against different Colletotrichum species indicate its potential as a fungicide for protecting various fruits against anthracnose disease-causing fungi.


Assuntos
Colletotrichum , Coprinus , Doenças das Plantas , Colletotrichum/efeitos dos fármacos , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Benzaldeídos/farmacologia , Antifúngicos/farmacologia , Fungicidas Industriais/farmacologia , Esporos Fúngicos/efeitos dos fármacos
14.
J Agric Food Chem ; 72(23): 12915-12924, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38807027

RESUMO

Plant pathogenic fungi pose a significant threat to agricultural production, necessitating the development of new and more effective fungicides. The ring replacement strategy has emerged as a highly successful approach in molecular design. In this study, we employed the ring replacement strategy to successfully design and synthesize 32 novel hydrazide derivatives containing diverse heterocycles, such as thiazole, isoxazole, pyrazole, thiadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, thiophene, pyridine, and pyrazine. Their antifungal activities were evaluated in vitro and in vivo. Bioassay results revealed that most of the title compounds displayed remarkable antifungal activities in vitro against four tested phytopathogenic fungi, including Fusarium graminearum, Botrytis cinerea, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound 5aa displayed a broad spectrum of antifungal activity against F. graminearum, B. cinerea, S. sclerotiorum, and R. solani, with the corresponding EC50 values of 0.12, 4.48, 0.33, and 0.15 µg/mL, respectively. In the antifungal growth assay, compound 5aa displayed a protection efficacy of 75.5% against Fusarium head blight (FHB) at a concentration of 200 µg/mL. In another in vivo antifungal activity evaluation, compound 5aa exhibited a noteworthy protective efficacy of 92.0% against rape Sclerotinia rot (RSR) at a concentration of 100 µg/mL, which was comparable to the positive control tebuconazole (97.5%). The existing results suggest that compound 5aa has a broad-spectrum antifungal activity. Electron microscopy observations showed that compound 5aa might cause mycelial abnormalities and organelle damage in F. graminearum. Moreover, in the in vitro enzyme assay, we found that the target compounds 5aa, 5ab, and 5ca displayed significant inhibitory effects toward succinate dehydrogenase, with the corresponding IC50 values of 1.62, 1.74, and 1.96 µM, respectively, which were superior to that of boscalid (IC50 = 2.38 µM). Additionally, molecular docking and molecular dynamics simulation results revealed that compounds 5aa, 5ab, and 5ca have the capacity to bind in the active pocket of succinate dehydrogenase (SDH), establishing hydrogen-bonding interactions with neighboring amino acid residues.


Assuntos
Ascomicetos , Botrytis , Desenho de Fármacos , Fungicidas Industriais , Fusarium , Doenças das Plantas , Rhizoctonia , Succinato Desidrogenase , Succinato Desidrogenase/antagonistas & inibidores , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Fungicidas Industriais/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Relação Estrutura-Atividade , Ascomicetos/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Rhizoctonia/efeitos dos fármacos , Doenças das Plantas/microbiologia , Simulação de Acoplamento Molecular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Testes de Sensibilidade Microbiana , Hidrazinas/farmacologia , Hidrazinas/química , Hidrazinas/síntese química , Estrutura Molecular , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Compostos Heterocíclicos/síntese química
15.
J Agric Food Chem ; 72(23): 13015-13022, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38807413

RESUMO

The extensive and repeated application of chemical fungicides results in the rapid development of fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources of pesticides. It is necessary to discover antifungal pesticides by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their antifungal activities were evaluated in vitro. Most of them showed good antifungal activity, especially 3d exhibited a very broad antifungal spectrum and the most significant activities against 7 phytopathogenic fungi. In vivo activity results suggested that 3d protected apples and tomatoes from serious infection by phytopathogenic fungi. These proved that 3d had the potential to be a natural product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis suggested that tubulin might be one of the action sites of 3d. It is reasonable to believe that griseofulvin derivatives are worth further development for the discovery of new pesticides.


Assuntos
Fungos , Fungicidas Industriais , Griseofulvina , Doenças das Plantas , Griseofulvina/farmacologia , Griseofulvina/química , Griseofulvina/síntese química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Doenças das Plantas/microbiologia , Relação Estrutura-Atividade , Fungos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Solanum lycopersicum/microbiologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química
16.
J Agric Food Chem ; 72(23): 13154-13163, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38780776

RESUMO

Finding safe and environmentally friendly fungicides is one of the important strategies in modern pesticide research and development. In this work, the antipathogenic effects of the fungus Trichaptum laricinum against the anthracnose pathogen Colletotrichum anthrisci were studied. The EtOAc extract of T. laricinum showed remarkable antifungal activity against C. anthrisci with an inhibition rate of 50% at 256 µg/mL. Bioguided isolation of the cultural broth of T. laricinum produced four new drimane sesquiterpenes, trichalarins A-D (1-4), and six other metabolites (5-10). Their structures were established by extensive spectroscopic methods, quantum chemical calculations, and single-crystal X-ray diffraction. All compounds exhibited antifungal activity against C. anthrisci with minimum inhibitory concentrations (MICs) of 8-64 µg/mL in vitro. Further in vivo assay suggested that compounds 2, 6, and 9 could significantly inhibit C. anthrisci growth in avocado fruit with inhibition rates close to 80% at the concentration of 256 µg/mL, while compounds 2 and 6 had an inhibition rate over 90% at the concentration of 512 µg/mL. The EtOAc extract of T. laricinum had no inhibitory effect on Pinus massoniana seed germination and growth at the concentration of 2 mg/mL, showing good environmental friendliness. Thus, the fungus T. laricinum could be considered as an ideal biocontrol strain, and its metabolites provided a diverse material basis for the antibiotic agents.


Assuntos
Colletotrichum , Fungicidas Industriais , Testes de Sensibilidade Microbiana , Doenças das Plantas , Colletotrichum/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Estrutura Molecular , Sesquiterpenos/farmacologia , Sesquiterpenos/química
17.
J Environ Sci Health B ; 59(6): 341-349, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709203

RESUMO

The increased consumption of pesticides can have a negative environmental impact by increasing the essential metals to toxic levels. Bordasul® is a commonly used fungicide in Brazil and it is composed of 20% Cu, 10% sulfur, and 3.0% calcium. The study of fungicides in vivo in non-target model organisms can predict their environmental impact more broadly. The Drosophila melanogaster is a unique model due to its ease of handling and maintenance. Here, the potential toxicity of Bordasul® was investigated by assessing the development, survival, and behavior of exposed flies. Exposure to Bordasul® impaired the development (p < 0.01) and caused a significant reduction in memory retention (p < 0.05) and locomotor ability (p < 0.001). Fungicides are needed to assure the world's food demand; however, Bordasul® was highly toxic to D. melanogaster. Therefore, Bordasul® may be potentially toxic to non-target invertebrates and new environmentally-safe biofertilizers have to be developed to preserve the biota.


Assuntos
Cobre , Drosophila melanogaster , Fungicidas Industriais , Animais , Drosophila melanogaster/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Fungicidas Industriais/farmacologia , Cobre/toxicidade , Brasil , Feminino , Masculino , Comportamento Animal/efeitos dos fármacos
18.
J Agric Food Chem ; 72(20): 11360-11368, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38720533

RESUMO

In this study, a series of acrylamide derivatives containing trifluoromethylpyridine or piperazine fragments were rationally designed and synthesized. Subsequently, the in vitro antifungal activities of all of the synthesized compounds were evaluated. The findings revealed that compounds 6b, 6c, and 7e exhibited >80% antifungal activity against Phomopsis sp. (Ps) at the concentration of 50 µg/mL. Furthermore, the EC50 values for compounds 6b, 6c, and 7e against Ps were determined to be 4.49, 6.47, and 8.68 µg/mL, respectively, which were better than the positive control with azoxystrobin (24.83 µg/mL). At the concentration of 200 µg/mL, the protective activity of compound 6b against Ps reached 65%, which was comparable to that of azoxystrobin (60.9%). Comprehensive mechanistic studies, including morphological studies with fluorescence microscopy (FM), cytoplasmic leakage, and enzyme activity assays, indicated that compound 6b disrupts cell membrane integrity and induces the accumulation of defense enzyme activity, thereby inhibiting mycelial growth. Therefore, compound 6b serves as a valuable candidate for the development of novel fungicides for plant protection.


Assuntos
Acrilamida , Desenho de Fármacos , Fungicidas Industriais , Piridinas , Fungicidas Industriais/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Acrilamida/química , Piridinas/química , Piridinas/farmacologia , Piridinas/síntese química , Relação Estrutura-Atividade , Ascomicetos/efeitos dos fármacos , Ascomicetos/crescimento & desenvolvimento , Piperazina/química , Piperazina/farmacologia , Piperazinas/farmacologia , Piperazinas/química , Piperazinas/síntese química , Estrutura Molecular , Testes de Sensibilidade Microbiana , Doenças das Plantas/microbiologia
19.
J Agric Food Chem ; 72(20): 11308-11320, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38720452

RESUMO

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 µg/mL that was superior to that of the agricultural fungicide boscalid (2.2 µg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 µM that was superior to that of boscalid (7.9 µM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.


Assuntos
Desenho de Fármacos , Inibidores Enzimáticos , Fungicidas Industriais , Oximas , Pirazóis , Succinato Desidrogenase , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/química , Succinato Desidrogenase/metabolismo , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Relação Estrutura-Atividade , Oximas/química , Oximas/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Proteínas Fúngicas/química , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/metabolismo , Simulação de Acoplamento Molecular , Rhizoctonia/efeitos dos fármacos , Éteres/química , Éteres/farmacologia , Estrutura Molecular
20.
J Agric Food Chem ; 72(20): 11415-11428, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38727515

RESUMO

Rice sheath blight, caused by the fungus Rhizoctonia solani, poses a significant threat to rice cultivation globally. This study aimed to investigate the potential mechanisms of action of camphor derivatives against R. solani. Compound 4o exhibited superior fungicidal activities in vitro (EC50 = 6.16 mg/L), and in vivo curative effects (77.5%) at 500 mg/L were significantly (P < 0.01) higher than the positive control validamycin·bacillus (66.1%). Additionally, compound 4o exhibited low cytotoxicity and acute oral toxicity for adult worker honeybees of Apis mellifera L. Mechanistically, compound 4o disrupted mycelial morphology and microstructure, increased cell membrane permeability, and inhibited both PDH and SDH enzyme activities. Molecular docking and molecular dynamics analyses indicated a tight interaction of compound 4o with PDH and SDH active sites. In summary, compound 4o exhibited substantial antifungal efficacy against R. solani, serving as a promising lead compound for further optimization of antifungal agents.


Assuntos
Cânfora , Fungicidas Industriais , Simulação de Acoplamento Molecular , Oryza , Doenças das Plantas , Rhizoctonia , Rhizoctonia/efeitos dos fármacos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Animais , Cânfora/farmacologia , Cânfora/química , Abelhas/microbiologia , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Relação Estrutura-Atividade
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