RESUMO
Azobenzene moieties can serve as active fragments in antimicrobials and exert trans/cis conversions of molecules. Herein, a series of novel nicotinamide derivatives (NTMs) were developed by employing a two-step strategy, including azo-incorporating and bioisosteric replacement. Azo-incorporation can conveniently provide compounds that can be easily optically interconverted between trans/cis isomers, enhancing the structural diversity of azo compounds. It is noteworthy that the replacement of the azo bond with a 1,2,4-oxadiazole motif through further bioisosteric replacement led to the discovery of a novel compound, NTM18, which made a breakthrough in preventing rice sheath blight disease. A control effect value of 94.44% against Rhizoctonia solani could be observed on NTM18, while only 11.11% was determined for boscalid at 200 mg·L-1. Further mechanism validations were conducted, and the molecular docking analysis demonstrated that compound NTM18 might have a tight binding with SDH via an extra π-π interaction between the oxadiazole ring and residue of D_Y586. This work sets up a typical case for the united applications of azo-incorporating and bioisosteric replacement in fungicide design, posing an innovative approach in structural diversity-based development of pesticides.
Assuntos
Compostos Azo , Fungicidas Industriais , Simulação de Acoplamento Molecular , Niacinamida , Oryza , Doenças das Plantas , Rhizoctonia , Niacinamida/química , Compostos Azo/química , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/química , Oryza/química , Oryza/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Twenty-two eco-friendly, novel Schiff bases were synthesized from 2,4,5-trichloro aniline and characterized by using FT-IR, 1H NMR, and 13C NMR techniques. Fungicidal activity against pathogenic fungi Sclerotium rolfsii and Rhizoctonia bataticola and insecticidal activity against the stored grain insect pest Callosobruchus maculatus of the test compounds were evaluated under control condition. All of the investigated compounds, according to the study, exhibited moderate to good antifungal and insecticidal activities. The best antifungal activity against both pathogenic fungi was demonstrated by C15 and C16 whose ED50 values were recorded 11.4 and 10.4 µg/mL against R. bataticola and 10.6 and 11.9 µg/mL against S. rolfsii, respectively. They were further screened in for disease suppression against both pathogenic fungi under pot condition through different methods of applications in green gram (Vigna radiata L.) crop. The compounds C10 and C18 had the highest insecticidal activity, with LD50 values of 0.024 and 0.042 percentages, respectively. Stepwise regression analysis using root mean square error (RMSE) and correlation coefficient (R) method used to validate the quantitative structure activity relationship (QSAR) of synthesized compounds in addition to their fungicidal and insecticidal actions. To the best of our knowledge, this investigation on the 22 new Schiff bases as possible agrochemicals is the first one that has been fully reported.
Assuntos
Rhizoctonia , Bases de Schiff , Vigna , Rhizoctonia/efeitos dos fármacos , Animais , Inseticidas/farmacologia , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Besouros/efeitos dos fármacosRESUMO
Using antifungal agrochemicals as the most economical solution might reduce plant diseases caused by pathogenic fungi, which have a significant negative impact on the quality and yield of food worldwide. In this work, 33 compounds (G) containing 1,2,3-triazole and malononitrile structures were synthesized. When the compounds were tested in vitro against six fungal species, they exhibited significant fungicidal activity toward Botrytis cinerea and Rhizoctonia solani. Compounds G17 and G30 displayed promising in vivo efficacy, with an EC50 of 0.19 and 0.27 mg/L respectively against R. solani. Fungal ergosterol production was suppressed by compounds G17 and G30, according to a preliminary analysis of their mechanism of action on R. solani using transcriptomics and scanning electron microscopy. It has been shown through experimentation that compounds G17 and G30 prevent R. solani from synthesizing ergosterol. Ultimately, it was anticipated that compounds G17 and G30 would be discovered to be low-toxic.
Assuntos
Botrytis , Fungicidas Industriais , Nitrilas , Rhizoctonia , Triazóis , Triazóis/química , Triazóis/farmacologia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Rhizoctonia/efeitos dos fármacos , Nitrilas/química , Nitrilas/farmacologia , Botrytis/efeitos dos fármacos , Desenho de Fármacos , Relação Estrutura-Atividade , Doenças das Plantas/microbiologia , Estrutura MolecularRESUMO
Sophora flavescens, a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC50 values ranging from 4.76 to 13.94 µg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with EC50 values of 16.12, 16.55, and 16.99 µg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea. It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea. Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.
Assuntos
Botrytis , Flavonoides , Fungicidas Industriais , Fusarium , Doenças das Plantas , Raízes de Plantas , Rhizoctonia , Sophora , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Sophora/química , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Fusarium/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Raízes de Plantas/química , Doenças das Plantas/microbiologia , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Prenilação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Sophora flavescensRESUMO
Five novel imidazole-functionalized chitosan derivatives 3a-3e were synthesized via addition reactions of chitosan with imidazole derivatives. The partial incorporation of imidazole moiety in chitosan were confirmed by FTIR, UV, 1H NMR, XRD, SEM and GPC. Meanwhile, the antifungal activity against three common plant pathogenic fungi: Phytophthora nicotianae (P. nicotianae), Fusarium graminearum (F. graminearum) and Rhizoctonia solani (R. solani), was assayed in vitro at 0.5 and 1.0 mg/mL by hyphal measurement, and the introduction of imidazole group can influence the antifungal activity. At 0.5 mg/mL, 3e inhibited P. nicotianae growth by 42 % and had an inhibitory index against R. solani of 50 %. Derivative 3e was more effective than unmodified chitosan whose antifungal index was 17 % against P. nicotianae and 22 % against R. solani. To our surprise, at 1.0 mg/mL, the inhibition rate of 3e against R. solani can reach 99 %, while the inhibition rate of chitosan is only 38 %. These results indicated that some imidazole chitosan derivatives with enhanced antifungal activities could serve as potential biomaterial for antifungal application.
Assuntos
Antifúngicos , Quitosana , Imidazóis , Testes de Sensibilidade Microbiana , Quitosana/química , Quitosana/farmacologia , Quitosana/síntese química , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/síntese química , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Fusarium/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Phytophthora/efeitos dos fármacosRESUMO
Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 novel benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange and a link approach as promising SDH inhibitors. The findings from the tests on antifungal activity indicated that most of the synthesized compounds displayed remarkable inhibition against the fungi tested. Compound Ig N-(2-(((5-chlorobenzo[d]thiazol-2-yl)thio)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-yrazole-4-carboxamide, with EC50 values against four kinds of fungi tested below 10 µg/mL and against Cercospora arachidicola even below 2 µg/mL, showed superior antifungal activity than that of commercial fungicide thifluzamide, and specifically compounds Ig and Im were found to show preventative potency of 90.6% and 81.3% against Rhizoctonia solani Kühn, respectively, similar to the positive fungicide thifluzamide. The molecular simulation studies suggested that hydrophobic interactions were the main driving forces between ligands and SDH. Encouragingly, we found that compound Ig can effectively promote the wheat seedlings and the growth of Arabidopsis thaliana. Our further studies indicated that compound Ig could stimulate nitrate reductase activity in planta and increase the biomass of plants.
Assuntos
Inibidores Enzimáticos , Fungicidas Industriais , Pirazóis , Succinato Desidrogenase , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/metabolismo , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Simulação de Acoplamento Molecular , Benzotiazóis/química , Benzotiazóis/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Ascomicetos/efeitos dos fármacos , Ascomicetos/enzimologia , Estrutura MolecularRESUMO
The diphenyl ether molecular pharmacophore has played a significant role in the development of fungicidal compounds. In this study, a variety of pyrazol-5-yl-phenoxybenzamide derivatives were synthesized and evaluated for their potential to act as succinate dehydrogenase inhibitors (SDHIs). The bioassay results indicate certain compounds to display a remarkable and broad-spectrum in their antifungal activities. Notably, compound 12x exhibited significant in vitro activities against Valsa mali, Gaeumannomyces graminis, and Botrytis cinerea, with EC50 values of 0.52, 1.46, and 3.42 mg/L, respectively. These values were lower or comparable to those of Fluxapyroxad (EC50 = 12.5, 1.93, and 8.33 mg/L, respectively). Additionally, compound 12x showed promising antifungal activities against Sclerotinia sclerotiorum (EC50 = 0.82 mg/L) and Rhizoctonia solani (EC50 = 1.86 mg/L), albeit lower than Fluxapyroxad (EC50 = 0.23 and 0.62 mg/L). Further in vivo experiments demonstrated compound 12x to possess effective protective antifungal activities against V. mali and S. sclerotiorum at a concentration of 100 mg/L, with inhibition rates of 66.7 and 89.3%, respectively. In comparison, Fluxapyroxad showed inhibition rates of 29.2 and 96.4% against V. mali and S. sclerotiorum, respectively. Molecular docking analysis revealed that compound 12x interacts with SDH through hydrogen bonding, π-cation, and π-π interactions, providing insights into the probable mechanism of action. Furthermore, compound 12x exhibited greater binding energy and SDH enzyme inhibitory activity than Fluxapyroxad (ΔGcal = -46.8 kcal/mol, IC50 = 1.22 mg/L, compared to ΔGcal = -41.1 kcal/mol, IC50 = 8.32 mg/L). Collectively, our results suggest that compound 12x could serve as a promising fungicidal lead compound for the development of more potent SDHIs for crop protection.
Assuntos
Ascomicetos , Benzamidas , Inibidores Enzimáticos , Proteínas Fúngicas , Fungicidas Industriais , Simulação de Acoplamento Molecular , Succinato Desidrogenase , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Relação Estrutura-Atividade , Benzamidas/farmacologia , Benzamidas/química , Ascomicetos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/química , Rhizoctonia/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Pirazóis/química , Pirazóis/farmacologia , Descoberta de Drogas , Estrutura Molecular , Doenças das Plantas/microbiologiaRESUMO
In the present investigation, we utilized zinc nanoparticles (Zn-NPs) and bacterial endophytes to address the dual challenge of heavy metal (HM) toxicity in soil and Rhizoctonia solani causing root rot disease of tomato. The biocontrol potential of Bacillus subtilis and Bacillus amyloliquefaciens was harnessed, resulting in profound inhibition of R. solani mycelial growth and efficient detoxification of HM through strong production of various hydrolytic enzymes and metabolites. Surprisingly, Zn-NPs exhibited notable efficacy in suppressing mycelial growth and enhancing the seed germination (%) while Gas chromatography-mass spectrometry (GC-MS) analysis unveiled key volatile compounds (VOCs) crucial for the inhibition of pathogen. Greenhouse trials underscored significant reduction in the disease severity (%) and augmented biomass in biocontrol-mediated plants by improving photosynthesis-related attributes. Interestingly, Zn-NPs and biocontrol treatments enhanced the antioxidant enzymes and mitigate oxidative stress indicator by increasing H2O2 concentration. Field experiments corroborated these findings, with biocontrol-treated plants, particularly those receiving consortia-mediated treatments, displayed significant reduction in disease severity (%) and enhanced the fruit yield under field conditions. Root analysis confirmed the effective detoxification of HM, highlighting the eco-friendly potential of these endophytes and Zn-NPs as fungicide alternative for sustainable production that foster soil structure, biodiversity and promote plant health.
Assuntos
Endófitos , Fotossíntese , Doenças das Plantas , Rhizoctonia , Solanum lycopersicum , Fotossíntese/efeitos dos fármacos , Endófitos/metabolismo , Rhizoctonia/crescimento & desenvolvimento , Rhizoctonia/efeitos dos fármacos , Solanum lycopersicum/microbiologia , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Zinco/metabolismo , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Bacillus amyloliquefaciens/metabolismo , Bacillus subtilis/metabolismo , Nanopartículas Metálicas/química , Oligoelementos/metabolismo , Microbiologia do Solo , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacosRESUMO
Plant diseases caused by pathogenic fungi seriously affect the yield and quality of crops, cause huge economic losses, and pose a considerable threat to global food security. Phenylpyrrole analogues were designed and synthesized based on alkaloid lycogalic acid. All target compounds were characterized by 1H NMR, 13C NMR, and HRMS. Their antifungal activities against seven kinds of phytopathogenic fungi were evaluated. The results revealed that most compounds had broad-spectrum fungicidal activities at 50 µg/mL; 14 compounds displayed more than 60% fungicidal activities against Rhizoctonia cerealis and Sclerotinia sclerotiorum, and in particular, the fungicidal activities of compounds 8g and 8h against Rhizoctonia cerealis were more than 90%, which could be further developed as lead agents for water-soluble fungicides. The molecular docking results indicate that compounds 8g and 8h can interact with 14α-demethylase (RcCYP51) through hydrogen bonding with strong affinity.
Assuntos
Alcaloides , Antifúngicos , Desenho de Fármacos , Simulação de Acoplamento Molecular , Pirróis , Rhizoctonia , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Pirróis/química , Pirróis/farmacologia , Pirróis/síntese química , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/síntese química , Rhizoctonia/efeitos dos fármacos , Relação Estrutura-Atividade , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ascomicetos/efeitos dos fármacosRESUMO
In this study, a series of novel hydrazide-containing flavonol derivatives was designed, synthesized, and evaluated for antifungal activity. In the in vitro antifungal assay, most of the target compounds exhibited potent antifungal activity against seven tested phytopathogenic fungi. In particular, compound C32 showed the best antifungal activity against Rhizoctonia solani (EC50 = 0.170 µg/mL), outperforming carbendazim (EC50 = 0.360 µg/mL) and boscalid (EC50 = 1.36 µg/mL). Compound C24 exhibited excellent antifungal activity against Valsa mali, Botrytis cinerea, and Alternaria alternata with EC50 values of 0.590, 0.870, and 1.71 µg/mL, respectively. The in vivo experiments revealed that compounds C32 and C24 were potential novel agricultural antifungals. 3D quantitative structure-activity relationship (3D-QSAR) models were used to analyze the structure-activity relationships of these compounds. The analysis results indicated that introducing appropriate electronegative groups at position 4 of a benzene ring could effectively improve the anti-R. solani activity. In the antifungal mechanism study, scanning electron microscopy and transmission electron microscopy analyses revealed that C32 disrupted the normal growth of hyphae by affecting the structural integrity of the cell membrane and cellular respiration. Furthermore, compound C32 exhibited potent succinate dehydrogenase (SDH) inhibitory activity (IC50 = 8.42 µM), surpassing that of the SDH fungicide boscalid (IC50 = 15.6 µM). The molecular dynamics simulations and docking experiments suggested that compound C32 can occupy the active site and form strong interactions with the key residues of SDH. Our findings have great potential for aiding future research on plant disease control in agriculture.
Assuntos
Alternaria , Botrytis , Flavonóis , Fungicidas Industriais , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Rhizoctonia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Alternaria/efeitos dos fármacos , Alternaria/crescimento & desenvolvimento , Flavonóis/farmacologia , Flavonóis/química , Doenças das Plantas/microbiologia , Estrutura Molecular , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/metabolismo , Ascomicetos/efeitos dos fármacos , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese químicaRESUMO
Bioisosteric silicon replacement has proven to be a valuable strategy in the design of bioactive molecules for crop protection and drug development. Twenty-one novel carboxamides possessing a silicon-containing biphenyl moiety were synthesized and tested for their antifungal activity and succinate dehydrogenase (SDH) enzymatic inhibitory activity. Among these novel succinate dehydrogenase inhibitors (SDHIs), compounds 3a, 3e, 4l, and 4o possessing appropriate clog P and topological polar surface area values showed excellent inhibitory effects against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Fusarium graminearum at 10 mg/L in vitro, and the EC50 values of 4l and 4o were 0.52 and 0.16 mg/L against R. solani and 0.066 and 0.054 mg/L against S. sclerotiorum, respectively, which were superior to those of Boscalid. Moreover, compound 3a demonstrated superior SDH enzymatic inhibitory activity (IC50 = 8.70 mg/L), exhibiting 2.54-fold the potency of Boscalid (IC50 = 22.09 mg/L). Docking results and scanning electron microscope experiments revealed similar mode of action between compound 3a and Boscalid. The new silicon-containing carboxamide 3a is a promising SDHI candidate that deserves further investigation.
Assuntos
Ascomicetos , Desenho de Fármacos , Fungicidas Industriais , Fusarium , Simulação de Acoplamento Molecular , Rhizoctonia , Silício , Succinato Desidrogenase , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Silício/química , Silício/farmacologia , Rhizoctonia/efeitos dos fármacos , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/metabolismo , Fusarium/efeitos dos fármacos , Relação Estrutura-Atividade , Ascomicetos/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Doenças das Plantas/microbiologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Estrutura Molecular , Amidas/química , Amidas/farmacologia , Amidas/síntese químicaRESUMO
A series of new piperidine-4-carbohydrazide derivatives bearing a quinazolinyl moiety were prepared and evaluated for their fungicidal activities against agriculturally important fungi. Among these derivatives, the chemical structure of compound A45 was clearly verified by X-ray crystallographic analysis. The antifungal bioassays revealed that many compounds in this series possessed good to excellent inhibition effects toward the tested fungi. For example, compounds A13 and A41 had EC50 values of 0.83 and 0.88 µg/mL against Rhizoctonia solani in vitro, respectively, superior to those of positive controls Chlorothalonil and Boscalid (1.64 and 0.96 µg/mL, respectively). Additionally, the above two compounds also exhibited notable inhibitory activities against Verticillium dahliae (with EC50 values of 1.12 and 3.20 µg/mL, respectively), far better than the positive controls Carbendazim and Chlorothalonil (19.3 and 11.0 µg/mL, respectively). More importantly, compound A13 could potently inhibit the proliferation of R. solani in the potted rice plants, showing good in vivo curative and protective efficiencies of 76.9% and 76.6% at 200 µg/mL, respectively. Furthermore, compound A13 demonstrated an effective inhibition of succinate dehydrogenase (SDH) activity in vitro with an IC50 value of 6.07 µM. Finally, the molecular docking study revealed that this compound could be well embedded into the active pocket of SDH via multiple noncovalent interactions, involving residues like SER39, ARG43, and GLY46.
Assuntos
Desenho de Fármacos , Fungicidas Industriais , Hidrazinas , Simulação de Acoplamento Molecular , Piperidinas , Rhizoctonia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Hidrazinas/química , Hidrazinas/farmacologia , Relação Estrutura-Atividade , Rhizoctonia/efeitos dos fármacos , Piperidinas/farmacologia , Piperidinas/química , Piperidinas/síntese química , Estrutura Molecular , Proteínas Fúngicas/química , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/metabolismo , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/metabolismo , Succinato Desidrogenase/química , Quinazolinas/farmacologia , Quinazolinas/química , Quinazolinas/síntese química , Testes de Sensibilidade MicrobianaRESUMO
Corn ear rot and fumonisin caused by Fusarium verticillioides pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The in vitro bioassay results indicated that compound 7c showed broad-spectrum in vitro activity with EC50 values falling from 3.51 to 24.10 µg/mL against Rhizoctonia solani and Alternaria solani, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound 7c also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 µg/mL. Fluorescence quenching and the molecular docking validated both 7c and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.
Assuntos
Alternaria , Fungicidas Industriais , Fusarium , Simulação de Acoplamento Molecular , Rhizoctonia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Alternaria/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Relação Estrutura-Atividade , Doenças das Plantas/microbiologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/química , Descoberta de Drogas , Zea mays/química , Zea mays/microbiologia , Estrutura MolecularRESUMO
Rice (Oryza sativa) stands as a crucial staple food worldwide, especially in Bangladesh, where it ranks as the third-largest producer. However, intensified cultivation has made high-yielding rice varieties susceptible to various biotic stresses, notably sheath blight caused by Rhizoctonia solani, which inflicts significant yield losses annually. Traditional fungicides, though effective, pose environmental and health risks. To address this, nanotechnology emerges as a promising avenue, leveraging the antimicrobial properties of nanoparticles like silver nanoparticles (AgNPs). This study explored the green synthesis of AgNPs using Ipomoea carnea leaf extract and silver nitrate (AgNO3), and also examined their efficacy against sheath blight disease in rice. The biosynthesized AgNPs were characterized through various analytical techniques such as UV-vis spectrophotometer, X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Particle size analyzer, Zeta potential, Scanning Electron Microscope (SEM), Field Emission Scanning Electron Microscope (FESEM), Transmission Electron Microscope (TEM) for confirming their successful production and crystalline nature of nanoparticles. The results of UV-visible spectrophotometers revealed an absorption peak ranging from 421 to 434 nm, validated the synthesis of AgNPs in the solution. XRD, DLS, and TEM estimated AgNPs sizes were ~45 nm, 66.2nm, and 46.38 to 73.81 nm, respectively. SEM and FESEM demonstrated that the synthesized AgNPs were spherical in shape. In vitro assays demonstrated the significant inhibitory effects of AgNPs on mycelial growth of Rhizoctonia solani, particularly at higher concentrations and pH levels. Further greenhouse and field experiments validated the antifungal efficacy of AgNPs against sheath blight disease in rice, exhibiting comparable effectiveness to commercial fungicides. The findings highlight the potential of AgNPs as a sustainable and effective alternative for managing rice sheath blight disease, offering a safer solution amidst environmental concerns associated with conventional fungicides.
Assuntos
Química Verde , Nanopartículas Metálicas , Oryza , Doenças das Plantas , Rhizoctonia , Prata , Rhizoctonia/efeitos dos fármacos , Oryza/microbiologia , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Difração de Raios X , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/químicaRESUMO
Nanocrop protectants have attracted much attention as sustainable platforms for controlling pests and diseases and improving crop nutrition. Here, we reported the fungicidal activity and disease inhibition potential of pectin-coated metal-iron organic framework nanoparticles (Fe-MOF-PT NPs) against rice stripe blight (RSB). An in vitro bacterial inhibition assay showed that Fe-MOF-PT NPs (80 mg/L) significantly inhibited mycelial growth and nucleus formation. The Fe-MOF-PT NPs adsorbed to the surface of mycelia and induced toxicity by disrupting cell membranes, mitochondria, and DNA. The results of a nontargeted metabolomics analysis showed that the metabolites of amino acids and their metabolites, heterocyclic compounds, fatty acids, and nucleotides and their metabolites were significantly downregulated after treatment with 80 mg/L NPs. The difference in metabolite abundance between the CK and Fe-MOF-PT NPs (80 mg/L) treatment groups was mainly related to nucleotide metabolism, pyrimidine metabolism, purine metabolism, fatty acid metabolism, and amino acid metabolism. The results of the greenhouse experiment showed that Fe-MOF-PT NPs improved rice resistance to R. solani by inhibiting mycelial invasion, enhancing antioxidant enzyme activities, activating the jasmonic acid signaling pathway, and enhancing photosynthesis. These findings indicate the great potential of Fe-MOF-PT NPs as a new RSB disease management strategy and provide new insights into plant fungal disease management.
Assuntos
Ferro , Estruturas Metalorgânicas , Oryza , Pectinas , Doenças das Plantas , Rhizoctonia , Oryza/metabolismo , Oryza/efeitos dos fármacos , Oryza/microbiologia , Rhizoctonia/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Ferro/química , Ferro/metabolismo , Pectinas/química , Pectinas/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/toxicidade , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Resistência à Doença/efeitos dos fármacosRESUMO
Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 µg/mL against G. zeae, EC50 = 1.01 µg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 µg/mL against A. alternata, EC50 = 0.20 µg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.
Assuntos
Antifúngicos , Testes de Sensibilidade Microbiana , Relação Quantitativa Estrutura-Atividade , Quinoxalinas , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Quinoxalinas/farmacologia , Quinoxalinas/química , Quinoxalinas/síntese química , Desenho de Fármacos , Alternaria/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Estrutura Molecular , Colletotrichum/efeitos dos fármacos , Gibberella/efeitos dos fármacosRESUMO
Pepper southern blight, caused by Sclerotium rolfsii, is a devastating soil-borne disease resulting in significant loss to pepper, Capsicum annuum L. production. Here, we isolated an antagonistic bacterial strain XQ-29 with antifungal activity against S. rolfsii from rhizospheric soil of pepper. Combining the morphological and biochemical characteristics with the 16S rDNA sequencing, XQ-29 was identified as Streptomyces griseoaurantiacus. It exhibited an inhibition of 96.83% against S. rolfsii and displayed significant inhibitory effects on Botrytis cinerea, Phytophthora capsica and Rhizoctonia solani. Furthermore, XQ-29 significantly reduced the pepper southern blight by 100% and 70.42% during seedling and growth stages, respectively. The antifungal mechanism involved altering the mycelial morphology, disrupting cell wall and membrane integrity, accompanied by accumulation of reactive oxygen species and lipid peroxidation in S. rolfsii mycelia. Furthermore, XQ-29 promoted growth and stimulated resistance of pepper plants by increasing defense-related enzyme activities and upregulating defense-related genes. Correspondingly, XQ-29 harbors numerous functional biosynthesis gene clusters in its genome, including those for siderophores and melanin production. The metabolic constituents present in the ethyl acetate extracts, which exhibited an EC50 value of 85.48 ± 1.62 µg/mL, were identified using LC-MS. Overall, XQ-29 demonstrates significant potential as a biocontrol agent against southern blight disease.
Assuntos
Botrytis , Capsicum , Doenças das Plantas , Rhizoctonia , Streptomyces , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Capsicum/microbiologia , Streptomyces/genética , Streptomyces/fisiologia , Botrytis/efeitos dos fármacos , Botrytis/fisiologia , Rhizoctonia/fisiologia , Rhizoctonia/efeitos dos fármacos , Basidiomycota/fisiologia , Phytophthora/fisiologia , Phytophthora/efeitos dos fármacos , Agentes de Controle Biológico/farmacologia , Antifúngicos/farmacologiaRESUMO
Rhizoctonia solani, the causal agent of banded leaf and sheath blight (BL&SB), poses a significant threat to maize and various crops globally. The increasing concerns surrounding the environmental and health impacts of chemical fungicides have encouraged intensified concern in the development of biological control agents (BCAs) as eco-friendly alternatives. In this study, we explored the potential of 22 rhizobacteria strains (AS1-AS22) isolates, recovered from the grasslands of the Pithoragarh region in the Central Himalayas, as effective BCAs against BL&SB disease. Among these strains, two Pseudomonas isolates, AS19 and AS21, exhibited pronounced inhibition of fungal mycelium growth in vitro, with respective inhibition rates of 57.04% and 54.15% in cell cultures and 66.56% and 65.60% in cell-free culture filtrates. Additionally, both strains demonstrated effective suppression of sclerotium growth. The strains AS19 and AS21 were identified as Pseudomonas sp. by 16S rDNA phylogeny and deposited under accession numbers NAIMCC-B-02303 and NAIMCC-B-02304, respectively. Further investigations revealed the mechanisms of action of AS19 and AS21, demonstrating their ability to induce systemic resistance (ISR) and exhibit broad-spectrum antifungal activity against Alternaria triticina, Bipolaris sorokiniana, Rhizoctonia maydis, and Fusarium oxysporum f. sp. lentis. Pot trials demonstrated significant reductions in BL&SB disease incidence (DI) following foliar applications of AS19 and AS21, with reductions ranging from 25 to 38.33% compared to control treatments. Scanning electron microscopy revealed substantial degradation of fungal mycelium by the strains, accompanied by the production of hydrolytic enzymes. These findings suggest the potential of Pseudomonas strains AS19 and AS21 as promising BCAs against BL&SB and other fungal pathogens. However, further field trials are warranted to validate their efficacy under natural conditions and elucidate the specific bacterial metabolites responsible for inducing systemic resistance. This study contributes to the advancement of sustainable disease management strategies and emphasizes the potential of Pseudomonas strains AS19 and AS21 in combating BL&SB and other fungal diseases affecting agricultural crops.
Assuntos
Doenças das Plantas , Pseudomonas , Rhizoctonia , Zea mays , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Zea mays/microbiologia , Pseudomonas/metabolismo , Rhizoctonia/fisiologia , Rhizoctonia/efeitos dos fármacos , Folhas de Planta/microbiologia , Agentes de Controle Biológico , Controle Biológico de Vetores/métodos , Antibiose , FilogeniaRESUMO
Rhizoctonia solani, the causative agent of sheath blight disease in rice, poses a significant threat to agricultural productivity. Traditional management approaches involving chemical fungicides have been effective but come with detrimental consequences for the ecosystem. This study aimed to investigate sustainable alternatives in the form of antifungal peptides derived from Solanaceous plant species as potential agents against R. solani. Peptide extracts were obtained using an optimized antimicrobial peptide (AMP) extraction method and desalted using the solid-phase extraction technique. The antifungal potential of peptide-rich extracts from Solanum tuberosum and Capsicum annum was assessed through in vitro tests employing the agar well diffusion method. Furthermore, peptide-protein docking analysis was performed on HPEPDOCK and HDOCK server; and molecular dynamics simulations (MDS) of 100 ns period were performed using the Gromacs 2020.4. The results demonstrated significant inhibition zones for both extracts at concentrations of 100 mg/mL. Additionally, the extracts of Solanum tuberosum and Capsicum annum had minimum inhibitory concentrations of 50 mg/mL and 25 mg/mL, respectively with minimum fungicidal concentrations of 25 mg/mL. Insights into the potential mechanisms of key peptides inhibiting R. solani targets were gleaned from in-silico studies. Notably, certain AMPs exhibited favorable free energy of binding against pathogenicity-related targets, including histone demethylase, sortin nexin, and squalene synthase, in protein-peptide docking simulations. Extended molecular dynamics simulations lasting 100 ns and MM-PBSA calculations were performed on select protein-peptide complexes. AMP10 displayed the most favorable binding free energy against all target proteins, with AMP3, AMP12b, AMP6, and AMP15 also exhibiting promising results against specific targets of R. solani. These findings underscore the potential of peptide extracts from S. tuberosum and C. annum as effective antifungal agents against rice sheath blight caused by R. solani.
Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Oryza , Doenças das Plantas , Rhizoctonia , Oryza/microbiologia , Doenças das Plantas/microbiologia , Rhizoctonia/efeitos dos fármacos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Solanum tuberosum/microbiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Solanaceae/química , Testes de Sensibilidade Microbiana , Simulação por Computador , Capsicum/microbiologia , Capsicum/químicaRESUMO
The development of new fungicide molecules is a crucial task for agricultural chemists to enhance the effectiveness of fungicides in agricultural production. In this study, a series of novel fluoroalkenyl modified succinate dehydrogenase inhibitors were synthesized and evaluated for their antifungal activities against eight fungi. The results from the in vitro antifungal assay demonstrated that compound 34 exhibited superior activity against Rhizoctonia solani with an EC50 value of 0.04 µM, outperforming commercial fluxapyroxad (EC50 = 0.18 µM) and boscalid (EC50 = 3.07 µM). Furthermore, compound 34 showed similar effects to fluxapyroxad on other pathogenic fungi such as Sclerotinia sclerotiorum (EC50 = 1.13 µM), Monilinia fructicola (EC50 = 1.61 µM), Botrytis cinerea (EC50 = 1.21 µM), and also demonstrated protective and curative efficacies in vivo on rapeseed leaves and tomato fruits. Enzyme activity experiments and protein-ligand interaction analysis by surface plasmon resonance revealed that compound 34 had a stronger inhibitory effect on succinate dehydrogenase compared to fluxapyroxad. Additionally, molecular docking and DFT calculation confirmed that the fluoroalkenyl unit in compound 34 could enhance its binding capacity with the target protein through p-π conjugation and hydrogen bond interactions.