Potential Fungicides Research Articles

L-Isoleucine-Derived Amide-hydrazide Compounds Evaluated as a Novel Potential Agricultural Fungicide

<scp>l</scp>-Isoleucine-Derived Amide-hydrazide Compounds Evaluated as a Novel Potential Agricultural Fungicide

Antifungal Activity of Novel Isoindoline-2-Yl Putrescines as Potential Autophagy-Activated Fungicide.

The exacerbation of plant fungal diseases necessitates the development of new fungicides to prevent outbreaks. In this study, five novel isoindoline-2-yl putrescines (ISPs) were synthesized, and their synthetic procedures and gram-scale preparation were explored. When tested at 50 μg mL-1, ISPs did not significantly inhibit mycelial growth on agar plates. However, at 100 μg mL-1, they demonstrated remarkable in vivo efficacy in mitigating Botrytis cinerea infection, especially ISP3 showed curative and protective activities of 91.9 % and 92.6 %, respectively. Moreover, ISP3 also effectively halted lesion expansion of gray mold, Sclerotic rot, and Fusarium scabs, while inducing excessive malformed top mycelial branches of B. cinerea and Sclerotinia sclerotiorum, suppressing sclerotia formation in S. sclerotiorum, and triggering autophagic vacuolization with numerous autophagosomes in the mycelia of these fungi. Molecular docking revealed that ISP3 effectively bound to the active site of BcAtg3, forming hydrogen bonds with Ser279, Gly343, Asp370, and Asp13, along with establishing a stable salt bridge with Asp13. Furthermore, ISP3 possessed favorable ADMET properties. These findings highlight ISP3 as a promising antifungal candidate through autophagy activation.

Synthesis and Fungicidal Activity Evaluation of Novel Triazole Thione/Thioether Derivatives Containing a Pyridylpyrazole Moiety.

Compounds containing N-pyridylpyrazole motif have aroused interest and brought about research hotspots due to their highly-efficient insecticidal activity. The fungicidal potential of N-pyridylpyrazole derivatives has gradually been disclosedin recent years. To discover new agrochemicals with poly-heterocyclic features, a series of novel triazole thione/thioether derivatives containing pyridylpyrazole motif (8-11) wassynthesized.The new compounds were identified by melting point, 1H NMR, 13C NMR, 19F NMR, HRMS,and elemental analysis. The bioassaysshowed that most of the pyridylpyrazole-containing triazole thione Mannich bases possessed favorable in vitrofungicidal activitytoward pathogenic fungi, such as Magnaporthe oryzae, Sclerotinia sclerotiorum, Botrytis cinerea andFusarium verticillioides, and were comparable with those of the contrast compounds Aand triadimefon. Some of them exhibited moderate to good in vivofungicidal activityagainst S. sclerotiorumat 0.2 mg/mL(e.g. 8fcontrol efficacy: 60.9±3.2%).The SEM observation displayed that 8f might cause disruptionof cell membrane and wall of S. sclerotiorum.Compounds 8a, 8c, 8f-8h, 8pand 9bcan serve as promising new fungicidal agents to make further structural optimization.The findings in this article provide useful clue and guidance for the design and development of new poly-heterocyclic agrochemicals.

Pathogen Composition and Fungicide Sensitivity in Rice Spikelet Rot Disease.

Rice spikelet rot disease (RSRD) is an emerging threat to rice crops, with sporadic but severe outbreaks in China in recent years. The composition of its pathogenic fungi has not been consistently identified, and chemical control methods remain unclear. This study aims to characterize the pathogen species responsible for RSRD and develop effective control strategies. Regional variations in disease symptoms and pathogen compositions were analyzed, which led to the identification of six novel pathogens, including Fusarium tanahbumbuense, Alternaria gaisen, Curvularia verruculosa, Curvularia brachyspora, Curvularia muehlenbeckiae, and Curvularia hominis. The pathogenic composition of RSRD exhibited considerable variation across different latitudes within China. Specifically, Alternaria spp. predominated in the Heilongjiang and Liaoning Provinces. Whereas Fusarium spp. and Curvularia spp. were more prevalent in the Hainan and Fujian Provinces. In contrast, Fusarium spp. and Alternaria spp. were the dominant pathogens in the Anhui and Jiangsu Provinces. Furthermore, an assessment of the sensitivity of these predominant pathogens to four chemical compounds was conducted, which led to the identification of potential fungicides for effective disease control. This research provides valuable insights into the pathogenic profile of RSRD across different regions and offers strategic recommendations for fungicide-based management of the disease.

Synthesis, Spectroscopy and Biological Studies of Copper and Silver Complexes Derived from 2-Substituted Amino Propanoic Acid

Synthesis of copper and silver complexes were prepared from novel Schiff base ligand. These synthesized ligand and their metal complexes were characterized by elemental analysis, FT-IR, 1H NMR, UV-Vis and Mass spectrometry. The coordination of amino nitrogen, phenolic oxygen, and carboxylato oxygen atoms is shown by the infrared spectra.The Schiff bases and its complexes were screened for their in vitro antibacterial and antifungal studies against the bacteria Pseudomonas Aeruginosa (PA, Gram -ve), Bacillus Cirroflagellosus (BC, Gram +ve), Penicillium Notatium (PN) and Aspergillus Niger (AN) strains. The results of the antibacterial investigation show that the copper and silver complexes possess more potent bactericide and fungicide properties than the ligand.

New binary mixtures of fungicides against Macrophomina phaseolina: Machine learning-driven QSAR, read-across prediction, and molecular dynamics simulation

Quantitative Structure-Activity Relationship (QSAR) analysis greatly enhances the development and research of pesticides. This study employed Multiple Linear Regression (MLR), machine learning (ML), and read-across (RA) approaches to investigate the combined effects of binary mixtures of fungicides on Macrophomina phaseolina. Using the Fixed Ratio Ray Design (FRRD) method, 75 binary mixtures of six frequently used fungicides were generated, with many exhibiting additive interactions as indicated by the Concentration Addition (CA) and Independent Action (IA) models. The QSAR analysis revealed that Support Vector Regression (SVR) and Gaussian Process Regression (GPR) models were the most effective, outperforming the Least Squares Kernel (LSK), MLR, and RA methods. SVR achieved an outstanding R2 of 0.95 and Q2LMO of 0.81, whereas GPR demonstrated values of 0.93 and 0.81 for the same metrics. Internal and external validation confirmed the reliability and generalizability of these models, suggesting they could be applied to a wider array of data. Moreover, Molecular Dynamics (MD) simulations showed that the effects of the fungicides are linked to physiological mechanisms rather than intermolecular interactions within their formulations. This study establishes a robust framework for creating potent fungicide combinations that improve disease management efficacy while promoting environmental sustainability and reducing the chemical load to mitigate negative impacts.

Antimicrobial activities of modified and unmodified pectin obtained from peels of Irvingia gabonensis, Cola milleni, and Theobroma cacao on specific pathogenic organisms

The antibacterial and antifungal activities of ethanolic extracts of pectin derived from the peels of Theobroma cacao, Cola milleni, and Irvingia gabonensis were investigated against phytopathogenic bacteria and fungi. The agar diffusion method was employed to test the extracts against Staphylococus aureus, Pseudomonas aeroginosa, Chromobacterium violaceum, Streptococcus feacalis, Xanthomonas axonopodis, Erwinia carotovora, Sclerotium rulfsii, Pythophthora palmivora, and Pyricularia oryzae. Significant differences (p&lt;0.05) were observed in all control groups. The extracts inoculated with Streptomycin exhibited the highest activity against all bacterial strains. Conversely, the unmodified extracts of pectin samples from cola, cocoa, and wild mango displayed the least inhibitory activity against the tested bacterial strains, while the modified extracts with Chloro Acetic Acid (CAA), Para Amino Benzoic Acid (PABA), and Para Nitro Benzoic Acid (PNBA) showed varying inhibitory effects. The control sample inoculated with Mancozeb demonstrated the highest zone of inhibition against all fungal strains in the three pectin samples. However, the modified pectin samples exhibited increased inhibitory effects compared to the unmodified pectin extract, although the results were closer to the control. The higher values of modified pectin can be attributed to the presence of modifying agents such as long-chain hydrocarbons, acetic acid, chloro compounds, carboxyl, benzene rings, amino groups, and nitro groups. The presence of secondary metabolites in the pectin samples may also contribute to the higher values observed in both modified and unmodified samples. Overall, the results indicate the fungicidal and bactericidal potential of the extracts against the tested organisms, suggesting their potential use as broad-spectrum antimicrobial agents.

Toxicity potential of a pyraclostrobin-based fungicide in plant and green microalgae models

ABSTRACT Pyraclostrobin-based fungicides play an effective role in controlling fungal diseases and are extensively used in agriculture. However, there is concern regarding the potential adverse effects attributed to exposure to these fungicides on non-target organisms and consequent influence exerted on ecosystem functioning. Thus, it is essential to conduct studies with model organisms to determine the impacts of these fungicides on different groups of living organisms. The aim of this study was to examine the ecotoxicity associated with exposure to commercial fungicides containing pyraclostrobin. The focus of the analysis involved germination and initial development of seedlings of 4 plant models (Lactuca sativa, Raphanus sativus, Pennisetum glaucum and Triticum aestivum), in addition to determining the population growth rate and total carbohydrate content in microalga Raphidocelis subcapitata. The fungicide pyraclostrobin adversely influenced growth and development of the tested plants, indicating a toxic effect. The fungicide exerted a significant impact on the initial development of seedlings of all model species examined with T. aestivum plants displaying the greatest susceptibility to pyraclostrobin. Plants of this species exhibited inhibitory effects on both aerial parts and roots when treated with a concentration of 4.75 mg/L pyraclostrobin. In addition, the green microalga R. subcapitata was also significantly affected by the fungicide, especially at relatively high concentrations as evidenced by a reduction in total carbohydrate content. This commercial fungicide demonstrated potential phytotoxicity for the tested plant models and was also considered toxic to the selected microalgae, indicating an ecotoxic effect that might affect other organisms in aquatic environments.

Novel Essential Oil-Based Thiosemicarbazone Compounds as Potential Fungicides in Controlling Postharvest Diseases of Citrus Fruit.

To develop novel fungicides for controlling postharvest fungal diseases in citrus fruits, 12 essential oil (EO)-based thiosemicarbazones compounds, termed hydrazine-carbothioamide, were prepared according to the condensation method. In vitro assays showed that compound 13j exhibited the strongest antifungal activity (minimum inhibitory concentration [MIC] = minimum fungicidal concentration [MFC] = 0.0125 mg/mL) against Penicillium digitatum. An in vivo study revealed that 5 × MFC of compound 13j can effectively mitigate the green mold incidence of citrus fruit inoculated with P. digitatum, as well as fruit rot during natural storage, at a level comparable to that of the chemical fungicide prochloraz. Throughout this process, fruit quality was maintained. The hemolysis assay showed that these thiosemicarbazone compounds have good biocompatibility and that their safety is comparable to that of prochloraz. The antifungal activity of compound 13j was attributed to membrane damage, as confirmed using scanning electron microscopy (SEM), Calcofluor white (CFW) staining, propidium iodide (PI) staining, Fourier transform-infrared (FT-IR) spectroscopy, optical density (OD)260, and relative conductivity assays. Collectively, our results indicate that compound 13j can be used as an antifungal agent to control the postharvest decay of citrus fruits.

Colchicine, Caffeine, Gramine, and Their Derivatives as Potential Herbicides, Fungicides, and Insecticides.

A preliminary in silico screening of 94 compounds, including colchicine, caffeine, gramine, and their derivatives, was conducted to identify potential herbicides, insecticides, and fungicides. Among the compounds tested, only gramine and its 13 derivatives exhibited potential activity. These compounds were further tested against eight species of insects, three species of weeds, and four species of fungi. All of the tested alkaloids were found to be ineffective as herbicides and insecticides, but they did exhibit some fungicidal activity. Four gramine derivatives showed some activity against Phytophthora infestans, Botrytis cinerea, Zymoseptoria tritici, and Fusarium culmorum.

Extraction and chemical constituents of the essential oils from Rosmarinus officinalis L. and Corymbia citriodora

The essential oils of Rosmarinus officinalis L. and Corymbia citriodora (Hook.) K.D.Hill &amp; L.A.S.Johnson leaves have chemical constituents with fungicide potential. The objective of this work was to determine the yield and the main chemical compounds of the essential oils of these species. Plants of the two species were georeferenced and collected in municipalities of Rio Grande do Sul, and identified in the Botany Laboratory of UNIJUÍ. The essential oils were extracted by hydrodistillation and the yield was based on fresh vegetable mass. The analyses of the chemical constituents were determined by CG-MS. A yield of 0.49% was obtained for R. officinalis and of 1.54% for C. citriodora. Similar to other studies, the major constituents of rosemary essential oil were camphor, 1,8-cineol, canfene and α-pineno, and the ones of eucalyptus essential oil were citronelal, isopulegol and citronelol. It is concluded that the chemical constituents are similar to those reported in the literature and the essential oil yield of the species is low and dependent on external conditions.

Synthesis, structural characterization, thermal analysis and antimicrobial assay of Co (II) complexes derived from benzaldehyde N4-substituted thiosemicarbazone

Microwave assisted Co (II) complexes of N4 -Substituted thiosemicarbazone were synthesized (TSC-La-f) and characterized by UV-visible spectra, IR spectra, 1H and 13C NMR spectra, elemental analysis, TGA, magnetic measurements and molar conductance. On the basis of spectral data, magnetic moment and thermal analysis square planar geometry assigned to Co(II) complexes. The electrolytic nature of the complexes was confirmed by their moderately high molar conductance values. All the metal complexes were screened for antimicrobial assay. Among all the complexes (TSC-Le) showed more activity than other Co (II) complexes. From this study it was concluded that complexes are more potent bactericide and fungicide than their corresponding ligands. Keywords: Thiosemicarbazones, benzaldehyde, Co(II) complexes, antimicrobial activity.

Synthesis and Antifungal Evaluation of Cinnamic Acid-Geraniol Hybrids as Potential Fungicides.

Cinnamic acid and geraniol are two well-known antifungal natural products and widely applied in food and cosmetics industries. To discover novel natural product-based fungicide candidates with more potent activity and good ecological compatibility for the management of plant diseases, a series of cinnamic acid-geraniol hybrids were prepared by means of molecular hybridization and their chemical structures were well confirmed by spectral analysis. The antifungal activities of the target compounds against three phytopathogenic fungi Fusarium graminearum, Gaeumannomycesgraminis (Sacc.) Arx et Oliver var. tritici (Sacc.) Walker, and Valsa mali were evaluated. Among them, compounds 5e and 5f showed the remarkable antifungal activity against G. graminis with the EC50 values of 82.719 and 91.828 μg/mL, respectively; while compounds 5f and 6b exhibited the obvious antifungal activity against V. mali. It suggested that compound 5f can be further optimized for the design of novel broad-spectrum fungicide molecules as the secondary lead compound. In addition, some interesting structure-antifungal activity relationships were obtained. This work will provide some reference and guidance for the further discovery of novel fungicide candidates based on cinnamic acid and geraniol.

Discovery of Aldehyde Dehydrogenase as a Potential Fungicide Target and Screening of its Natural Inhibitors against Fusarium verticillioides.

Fusarium verticillioides is the primary pathogen causing ear rot and stalk rot in corn (Zea mays). It not only affects yields but also produces mycotoxins endangering both human and animal health. Aldehyde dehydrogenase (ALDH) is essential for the oxidation of aldehydes in living organisms, making it a potential target for human drug design. However, there are limited reports on its function in plant pathogenic fungus. In this study, we analyzed the expression levels and gene knockout mutants, revealing that ALDH genes FvALDH-43 and FvALDH-96 in F. verticillioides played significant roles in pathogenicity and resistance to low-temperature stress by affecting antioxidant capacity. Virtual screening for natural product inhibitors and molecular docking were performed targeting FvALDH-43 and FvALDH-96. Following the biological activity analysis, three natural flavonoid compounds featuring a 2-hydroxyphenol chromene were identified. Among these, Taxifolin exhibited the highest biological activity and low toxicity. Both in vitro and in vivo biological evaluations confirmed that Taxifolin targeted ALDH and inhibited its activity. These findings indicate that aldehyde dehydrogenase may serve as a promising target for the design of novel fungicides.

Nanoencapsulation enhances the antimicrobial and antioxidant stability of cyclic lipopeptides for controlling Fusarium graminearum

Fusarium graminearum not only causes Fusarium head blight (FHB) on wheat but also produces fungal toxins that pose a serious threat to food safety. Biological control is one of the safe and most effective alternative methods. In this study, cyclic lipopeptides (CLPs) produced from Bacillus mojavensis B1302 were extracted and identified by LC-MS/MS. After preparing mesoporous silica nanoparticles-NH2 (MSNsN) and encapsulating CLPs, the characterization analysis showed that the interaction between CLPs and MSNsN enhanced the crystal structure of CLPs-MSNsN. The antimicrobial activity and antioxidant capacity of CLPs-MSNsN stored at 20 °C and 45 °C were decreased more slowly than those of free CLPs with increasing storage time, indicating the enhancement of the antimicrobial and antioxidant stability of CLPs. Moreover, the field control efficacy of long-term stored CLPs-MSNsN only decreased from 78.66% to 63.2%, but the efficacy of free CLPs decreased significantly from 84.34% to 26.01%. The deoxynivalenol (DON) content of wheat grains in the CLPs-MSNsN treatment group was lower than that in the free CLPs treatment group, which showed that long-term stored CLPs-MSNsN reduced the DON content in wheat grains. Further analysis of the action mechanism of CLPs-MSNsN on F. graminearum showed that CLPs-MSNsN could disrupt mycelial morphology, cause cell apoptosis, lead to the leakage of proteins and nucleic acids, and destroy the cell permeability of mycelia. This work puts a novel insight into the antimicrobial and antioxidant stability enhancement of CLPs-MSNsN through encapsulation and provides a potential fungicide to control F. graminearum, reduce toxins and ensure food safety.

CS and ZnO Nanoparticles as Fungicides against Potato Fungal Pathogens Alternaria solani and Fusarium solani. Mechanism Underlining Their Antifungal Activity

Fusarium solani (F. solani) and Alternaria solani (A. solani) are among the most destructive pathogenic fungi affecting potatoes, causing significant crop losses in both field and post-harvest conditions. Current control relies heavily on synthetic fungicides which pose serious environmental and health risks. Therefore, there is a growing need to find efficient and environmentally friendly alternatives to combat fungal infections in potatoes. This study offers chitosan (CS) and zinc oxide (ZnO) nanoparticles (NPs) as potential fungicides against A. solani and F. solani. We evaluated their antifungal properties and elucidated the mechanism underlining their activity. Our results revealed that both CS and ZnO NPs exhibited pronounced antifungal activity against the two pathogenic strains by effectively inhibiting the mycelium growth. Furthermore, we discovered that the activity of the NPs involved the induction of oxidative stress in fungal cells and changes in the molecular organization of their membranes.

Discovery of Novel Oxathiapiprolin Derivatives as Potent Fungicide Candidates.

Oxathiapiprolin (OXA), which targets the oxysterol-binding protein (OSBP), is an outstanding piperidinyl thiazole isoxazoline (PTI) fungicide that can be used to control oomycetes diseases. In this study, starting from the structure of OXA, a series of novel OSBP inhibitors were designed and synthesized by introducing an indole moiety to replace the pyrazole in OXA. Finally, compound b24 was found to exhibit the highest control effect (82%) against cucumber downy mildew (CDM) in the greenhouse at a very low dosage of 0.069 mg/L, which was comparable to that of OXA (88%). Furthermore, it showed better activity against potato late blight (PLB) than other derivatives of indole. The computational results showed that the R-conformation of b24 should be the dominant conformation binding to PcOSBP. The results of the present work indicate that the 3-fluorine-indole ring is a favorable fragment to increasing the electronic energy when binding with PcOSBP. Furthermore, compound b24 could be used as a lead compound for the discovery of new OSBP inhibitors.

Novel mandelic acid derivatives containing piperazinyls as potential candidate fungicides against Monilinia fructicola: Design, synthesis and mechanism study

Brown rot of stone fruit, a disease caused by the ascomycete fungus Monilinia fructicola, has caused significant losses to the agricultural industry. In order to explore and discover potential fungicides against M. fructicola, thirty-one novel mandelic acid derivatives containing piperazine moieties were designed and synthesized based on the amide skeleton. Among them, target compound Z31 exhibited obvious in vitro antifungal activity with the EC50 value of 11.8 mg/L, and significant effects for the postharvest pears (79.4 % protective activity and 70.5 % curative activity) at a concentration of 200 mg/L. Antifungal activity for the target compounds was found to be significantly improved by the large steric hindrance of the R1 groups and the electronegative of the piperazines in the molecular structure, according to a three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis. Further mechanism studies have demonstrated that the compound Z31 can disrupt cell membrane integrity, resulting in increased membrane permeability, release of intracellular electrolytes, and affect the normal growth of hyphae. Additional, morphological study also indicated that Z31 may disrupt the integrity of the membrane by inducing generate excess endogenous reactive oxygen species (ROS) and resulting in the peroxidation of cellular lipids, which was further verified by the detection of malondialdehyde (MDA) content. These studies have provided the basis for the creation of novel fungicides to prevent brown rot in stone fruits.

Antifungal Activity of Sesamol on Pestalotiopsis neglecta: Interfering with Cell Membrane and Energy Metabolism.

This paper investigated the inhibitory effect of Sesamol (Ses) on Pestalotiopsis neglecta. The potential inhibitory mechanisms were explored by observing changes in cell morphology, measuring alterations in cell membrane-related indices, as well as energy metabolism-related indices and changes in enzyme activities related to virulence. The results show that Ses completely inhibited the growth of P. neglecta at 600 μg/mL (minimum inhibitory concentration and minimum fungicidal concentration), with an EC50 of 142 ± 13.22 μg/mL. As observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Ses treatment resulted in the breakage and crumpling of P. neglecta cell membrane and organelle lysis. Ergosterol content and the total lipid in P. neglecta treated with 300 μg/mL Ses was 91.52% and 54% of that in the control groups, respectively. In addition, spores were stained, increased leakage of intracellular constituents at 260 nm, and decreased extracellular pH. This suggests damage to the cell membrane integrity and permeability. Furthermore, Ses decreased the ATP levels and key enzymes in the tricarboxylic acid (TCA) cycle, indicating interference with the fungal energy metabolism. Moreover, the activities of polygalacturonase (PG) and endoglucanase (EG) of P. neglecta treated with 300 μg/mL of Ses were only 28.20% and 29.13% of that in the control groups, respectively, indicating that Ses can reduce the virulence of P. neglecta. In conclusion, our results show that Ses should be considered as a potential plant-derived fungicide due to its ability to disrupt the morphology of P. neglecta, damage cell membrane integrity and permeability in P. neglecta, interfere with energy metabolism, and reduce its virulence, ultimately affecting the fungal growth.

Molecular Mechanism of Fusarium Fungus Inhibition by Phenazine-1-carboxamide.

Fusarium head blight caused by Fusarium graminearum is a devastating disease in wheat that seriously endangers food security and human health. Previous studies have found that the secondary metabolite phenazine-1-carboxamide produced by biocontrol bacteria inhibited F. graminearum by binding to and inhibiting the activity of histone acetyltransferase Gcn5 (FgGcn5). However, the detailed mechanism of this inhibition remains unknown. Our structural and biochemical studies revealed that phenazine-1-carboxamide (PCN) binds to the histone acetyltransferase (HAT) domain of FgGcn5 at its cosubstrate acetyl-CoA binding site, thus competitively inhibiting the histone acetylation function of the enzyme. Alanine substitution of the residues in the binding site shared by PCN and acetyl-CoA not only decreased the histone acetylation level of the enzyme but also dramatically impacted the development, mycotoxin synthesis, and virulence of the strain. Taken together, our study elucidated a competitive inhibition mechanism of Fusarium fungus by PCN and provided a structural template for designing more potent phenazine-based fungicides.