Fungicidal Compounds Research Articles

In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans

Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century. Traditional methods, such as fungicides, have drawbacks including high cost, restrictions on organic farming, potential risks to the environment and human health, and the development of resistant strains. In this study, we employed cutting-edge computer-based techniques, including Quantitative Structure-Activity Relationship (QSAR) modeling and molecular docking simulations, to uncover new fungicidal compounds and gain insights into their specific mechanisms of action against P. infestans. QSAR modeling on the number of compounds tested as P. infestans inhibitors was performed using an interactive OCHEM web platform. The predictive ability of the developed classification models had a balanced accuracy (BA) of 77–85 % for the training set and BA = 89–93 % for the validation external test set. During the in vitro testing against P. infestans, thirteen synthesized 2-oxoimidazolidine-4-sulfonamides demonstrated inhibition rates, ranging from 23.6 % to 87.4 %. The fungicidal potential of six of these fungicides ranged from 79.3 % to 87.4 %, which is comparable to the activity of known fungicides. Acute toxicity results using the well-known aquatic marker Daphnia magna showed that the most active sulfonamides 3d, 3f, 3h, 3j, 3k, and 3l, with LC50 values ranging from 13.7 to 52.9 mg/L, are low-toxicity compounds. The molecular docking results demonstrated a potential mechanism of the antifungal action of the studied 2-oxoimidazolidin-4-sulfonamide derivatives via the inhibition of fungal CYP51, a sterol biosynthesis enzyme.

Saccharomyces cerevisiae CCMA 0159 showed a high capacity to inhibit OTA-producing Aspergillus species.

The use of yeast to biologically control the production of ochratoxin A, which is caused by filamentous fungal growth, in coffee farms is a promising alternative to conventional methods. However, yeast strains, environmental field conditions, and the chemical composition of grains / fruits can influence the effectiveness of biological control agents. We tested the efficiency of different yeast strains in controlling three species of ochratoxigenic fungi in a coffee-based medium. The reasons and mechanisms behind the varying sensitivities of different Aspergillus species to biological control remains unclear. Aspergillus carbonarius rapidly assimilated carbon sources, giving it an advantage over yeasts in substrate colonisation. Saccharomyces cerevisiae CCMA 0159 inhibited all three fungal species, achieving efficiencies of 74.4%, 100%, and 80.9% against A. carbonarius, A. westerdijkiae, and A. ochraceus, respectively. The strategies employed by S. cerevisiae CCMA 0159 to inhibit the growth of ochratoxigenic fungi included competition, production of fungicidal volatile compounds, and alteration of the substrate's physicochemical properties. Our results indicate that among the yeast isolates tested, S. cerevisiae CCMA 0159 is the most effective in inhibiting ochratoxigenic fungi in coffee, including the more resistant A. carbonarius.

Discovery, Optimization, and Biological Evaluation of Novel Pyrazol-5-yl-phenoxybenzamide Derivatives as Potent Succinate Dehydrogenase Inhibitors.

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.

Regioselective Synthesis of Multisubstituted Fluoropyrazoles via Silver‐Catalyzed One‐Pot Cyclization Reaction of Diazo Reagents with Fluoronitroalkenes

AbstractA silver‐catalyzed regioselective one‐pot cyclization reaction of diazo reagents with fluoronitroalkenes was developed. This transformation presents a method for accessing a series of 4‐aryl‐3‐fluoropyrazoles that are substituted with various groups such as trifluoromethyl, carboxylic ester, nitrile, and phosphonate ester. Further synthetic transformations offered the corresponding fluorinated and trifluoromethylated analogues of two fungicide compounds.

Green Synthesis of Silver Nanoparticles with Hyssopus officinalis and Salvia officinalis Extracts, Their Properties, and Antifungal Activity on Fusarium spp.

Recent focus has been given to nanoparticles as an alternative fungicidal compound instead of chemical ones. More environmentally friendly ways of synthesis are the highest priority regarding the antifungal agents in the agriculture sector. Therefore, in this research, hyssop (H. officinalis) and sage (S. officinalis) aqueous extracts were prepared and used as a reducing source in the green synthesis of silver nanoparticles (AgNPs). Aqueous extracts and green synthesized AgNPs were examined for phytochemical composition and antioxidant capacity. Hyssop and sage extracts based AgNPs were analyzed using UV-vis spectrometry, SEM-EDS, and TEM-EDS. Antifungal activity against Fusarium spp. isolates collected from different infected crops was determined. Fusarium spp. isolates from strawberry, asparagus, pea, carrot, wheat, and rapeseed samples identified at the molecular level by translation elongation factor 1-alpha (TEF1α) gene amplification and sequencing. Green synthesized AgNPs had lower phytochemical content, however higher antioxidant activity compared to pure extracts. Both hyssop and sage extracts are suitable reducing agents for AgNPs formation, and sage extract results in larger particle size. Aqueous hyssop extract had higher antifungal activity than aqueous sage extract. However, a 10% concentration of whole sage extract based AgNPs solution, added to the PDA medium, and a 5% concentration of hyssop extract based AgNPs inhibited Fusarium spp. the most. F. proliferatum was the most sensitive to all treatments among the other fungi.

Fungicide compound 2, 3-dichloronaphthalene-1, 4-dione: Non-covalent interactions (QTAIM, RDG and ELF), combined vibrational spectroscopic investigations using DFT approach with experimental analysis, electronic, molecular docking scrutiny in-vitro assay and thermodynamic property analysis

Structural features and intramolecular interactions have been investigated with quantum mechanical calculations using DFT at the B3LYP level using a 6-311G(d,p) basis set. The study employed several spectroscopic techniques, such as FT-IR, FT-Raman, and UV–Vis, to investigate the molecular structure of 2,3-dichloronaphthalene-1,4-dione (DCND). An energy of 14.82 kJ/mol is required to stabilize the connection between the LP(Cl13) and the antibonding C8-C7, which suggests significant delocalization. The TDM analysis reveals plots demonstrating the ability to transmit charges. In ALIE analysis blue is employed to depict the stable sigma bonds, which tend to be tied to hydrogen atoms that generate protons. Achieving drug-likeness and ADMET assessment allowed for the biological characteristics of DCND to be evaluated. For docking analysis, the most potent inhibitor, 4YNU, is particularly remarkable since it can form up to five C–H–O hydrogen bonds yielding a binding energy of −6.4 kcal/mol.

Virtual screening of potential biofungicide candidate for sustainable fungal disease control

Captafol is widely used as a fungicide compound. However, it is banned in Thailand due to its carcinogen risk level. This study aimed to search for a potential biofungicide candidate via a computational approach to compensate the using of chemical fungicide. Based on the goal, natural compounds showing structures and properties similar to those of captafol were retrieved from various databases. The fungicide-likeness properties were screened. The binding pocket of chitin synthase I was identified, after which virtual screening was performed by AutoDock Vina, and interaction patterns were analysed by Discovery Studio. Finally, kaurane-16,18-diol 18-acetate (NPC132839) extracted from plants was selected as a potential biofungicide candidate with -7.0 kcal/mol of binding energy. The outcomes of this study could be utilised as a highly useful resource to increase the successful exposure of bioactive compounds of plant extracts without damage the environment.

Newly Evolved Different Fungicide Combinations against Paddy Sheath Blight under Field Conditions in West Bengal

Rice (Oryza sativa L.) is a vital global food crop, consumed by over half the world’s population. In India, it covers 43.5 M ha, yielding 112.9 Mt at a productivity of 2.56 t ha-1. In West Bengal, it spans 5.15 M ha, producing 15.09 Mt with a high productivity of 2933 kg ha-1. Rice sheath blight, caused by Rhizoctonia solani (also known as Thanatephorus cucumeris), is a highly destructive disease that has led to significant output losses in the last two decades. Reports suggest that production losses due to this disease can range from 5.2% to 50%, depending on factors like environmental conditions, crop growth stages, management practices, and rice cultivars used. This disease is called “sheath blight” because it initially infects the leaf sheath. To combat this disease, various fungicide compounds with diverse modes of action are available on the market. The research aimed to identify the most effective and cost-efficient fungicide combination for managing rice sheath blight. The experiment evaluated the efficacy and economics of Mancozeb 52.6% + Hexaconazole 2.4%, Hexaconazole 5% EC, and Hexaconazole 4% + Zineb 68%, as well as Mancozeb 75% WP under field conditions. The results showed that Mancozeb 52.6% + Hexaconazole 2.4% achieved the highest disease reduction over the control (46.10%), followed by Hexaconazole 5% EC (42.30%).

Isolation of active metabolites of B. ginsengihumi M2.11 with fungicidal activity

The purpose of this work is to purify and identify compounds from Bacillus ginsengihumi M2.11 that have fungicidal activity. Isolation of active metabolites was carried out by sample preparation, concentration, and chromatography. Substances were identified using a Maxsis impact mass spectrometer (Bruker). The results obtained were processed in the DataAnalysis Version 4.1 program. We searched library databases presented on the servers http://www.massbank.jp; http://www.chemspider.com. The most likely substance with fungicidal activity is a compound with m/z 1079, which is a lipopeptide. In this work, the fungicidal compound produced by the strain B. ginsengihumi M2.11 is a biosurfactant – disodium surfactin, with molecular formula C53H91N7Na2O13. Thus, the biocontrol function of the B. ginsengihumi M2.11 strain is largely determined by the secretion of surfactants – biosurfactants. Studying the mechanisms and modes of action of the active compound will allow full use in agriculture to protect plants from phytopogens, increase the quality and quantity of yield.

Occidiofungin inhibition of Candida biofilm formation on silicone elastomer surface.

Biofilms are the leading cause of clinically acquired fungal infections and contribute to significantly high morbidity and mortality in immunocompromised and hospitalized patients. Candida biofilms exhibit increased resistance to currently available antifungal agents that contribute to persistent reoccurring infections and are driving efforts to identify novel fungicidal compounds. The natural product, occidiofungin, is an antifungal compound with demonstrated activity against hyphal morphogenesis in polymorphic Candida species. In this study, we use an in vitro static biofilm model to demonstrate the efficacy of occidiofungin against C. albicans and C. tropicalis at all stages of biofilm development, including inhibiting cell dispersal. Consistent with prior findings, we demonstrate that actin organization is altered following occidiofungin exposure to include loss of F-actin cables and accumulation of actin aggregates. Altogether, our results provide strong evidence of the antibiofilm activity of occidiofungin toward Candida biofilms and support its potential as a therapeutic for Candida infections. IMPORTANCE Candida are opportunistic fungal pathogens with medical relevance given their association with superficial to life-threatening infections. An important component of Candida virulence is the ability to form a biofilm. These structures are highly resistant to antifungal therapies and are often the cause of treatment failure. In this work, we evaluated the efficacy of the antifungal compound, occidiofungin, against Candida biofilms developed on a silicone surface. We demonstrate that occidiofungin eliminated cells at all stages of biofilm formation in a dose-dependent manner. Consistent with our understanding of occidiofungin bioactivity, we noted alterations to actin organization and cell morphology following antifungal exposure. Given the challenges associated with the treatment of biofilm-associated infections, occidiofungin exhibits potential as a therapeutic antifungal agent in the future.

Molecular Insights into the Covalent Binding of Zoxamide to the β-Tubulin of Botrytis cinerea.

Botrytis cinerea is a fungal plant pathogen that causes significant economic losses in the agricultural industry worldwide. Fungicides that target microtubules, such as carbendazim (CBZ), diethofencarb (DEF), and zoxamide (ZOX), are widely used in crop protection against this pathogen. These groups of compounds exert their fungicidal activity by disrupting the microtubule assembly by binding to the β-tubulin subunit, provoking cell-cycle arrest and cell death. However, with the appearance of isolates resistant to these compounds, it is necessary to search for new alternatives to control this pathogenic fungus. In this work, we gained insight into the binding and stability of these fungicides in the benzimidazole binding site of B. cinerea β-tubulin through different computational approaches. Our molecular dynamics simulation replicas showed that R enantiomers of ZOX and its analog RH-4032 had better interaction profiles at the site compared to S enantiomers. The simulations also revealed that while the R-isomer fungicides formed H-bonds with the main chain carbonyl of V236 or the side chain residue of S314, only CBZ interacted with E198. Previous experimental data have identified key mutations in B. cinerea's β-tubulin gene that lead to the development of resistance or, on the contrary, increased sensitivity for treatment with these fungicide compounds. In agreement with experimental findings, alchemical free energy calculations showed that E198A and E198V mutations in B. cinerea β-tubulin have high sensitivity to (R)-ZOX, whereas the E198K mutation decreased its affinity. Similarly, the results obtained explain the resistance to CBZ of B. cinerea isolates with E198A/V/K mutations and the insensitivity of the wild-type organism to DEF. Our work provides a deeper insight into the molecular mechanism of action of these fungicides, highlighting the importance of understanding the interaction profiles to develop more effective antifungal agents.

Design, Synthesis, and Antifungal Activity of Novel 2-Ar-1,2,3-Triazole Derivatives.

Triazoles are crucial molecular frameworks in the development of fungicidal compounds. Although there has been extensive research on triazole derivatives for fungicide discovery, the investigation of 2-Ar-substituted-1,2,3-triazoles remains in progress. This study reports the synthesis and evaluation of the fungicidal activity of 27 distinct 2-Ar-substituted-1,2,3-triazole derivatives. These derivatives were synthesized from anilines through a three-step process, with the key step being the Cu(II)-catalyzed annulation reaction of readily accessible alkyl 3-aminoacrylates with aryldiazonium salts. All derivatives were novel, and their structures were characterized using 1H NMR, 13C NMR, and high-resolution mass spectrometry. Their antifungal activity was tested against five phytopathogenic fungi. Twelve of the target compounds exhibited better performance than the positive control hymexazol in the fungal test. Notably, compound 6d demonstrated the most potent inhibition against Botryosphaeria dothidea with an EC50 value of 0.90 mg/L. The structure-activity relationships are also discussed in this paper. Preliminary studies on the antifungal mechanism of compound 6d revealed that it inhibits ergosterol synthesis and alters the morphology and ultrastructure of the B. dothidea mycelium. These results suggest that the designed 2-Ar-substituted-1,2,3-triazole-containing hydrazone derivatives warrant further investigation as potential lead compounds for novel antifungal agents.

<i>Rhizoctonia solani</i> AG5 and its offspring – Morphology and sensitivity to fungicides

These studies aimed to identify differences and similarities within the progeny of <i>Rhizoctonia solani</i> AG5, which arose from basidiospores produced by the maternal strain ID23. The following characteristics were analyzed: the appearance of the mycelium (color, structure, zonation, and presence of sclerotia), growth rate (at 10°C, 20°C, and 30°C), fungicide sensitivity, and hyphal structure. The mycelial color of <i>R. solani</i> AG5 ranged from white/cream to light and dark brown. The structure of the mycelium may be compacted or flattened with visible zoning or fluffy with dark brown sclerotia on the colony surface. Homokaryons and heterokaryons derived from homokaryons were analyzed by constructing a phylogenetic tree using morphological data. Single basidiospore-grown isolates formed a separate subclade, most of which were grouped with a maternal isolate; however, heterokaryons derived from them created a separate subclade. In addition, isolates grown in basidiospores germinated at low temperatures created their own group, but with some exceptions. This shows a divergence in the morphological parameters of the subsequent generations and within generations. The optimal temperature for growth was found to be between 20°C and 30°C. The exceptions were strains obtained from basidiospores that germinated at refrigerated temperatures. For these samples, 10°C was found to be the optimal growth temperature. The hyphae of homokaryons were characterized by branching at an almost right angle and a septum at the site of constriction of the branch itself. The mean diameter of hyphae ranged from 2.93–15.60 μm, depending on the age of the hyphae. The fungicidal compounds at a concentration of 10 ppm had no significant effect on the activity of the tested strains, whereas a tenfold increase in the dose reduced the growth ability of the tested isolates. The activity of fungicides containing azoxystrobin, thiuram, or thiophanate-methyl on <i>R. solani</i> resulted in a reduction in the mycelial growth rate only in the case of azoxystrobin and thiuram, and in some cases, it was completely inhibited (thiophanate-methyl).

Effects of salicylic acid-grafted bamboo hemicellulose on gray mold control in blueberry fruit: The phenylpropanoid pathway and peel microbial community composition

Bamboo hemicellulose (HC) is a natural plant polysaccharide with good biocompatibility and biodegradability. But its poor antibacterial activity limits its application in fruits preservation. In this study, based on the good inducer of salicylic acid (SA) for plant diseases resistance, a novel antibacterial coating material was synthesized by grafting SA onto HC. The study aimed to investigate the synergistic effect of HC-g-SA on antibacterial ability, induces diseases resistance and microbial community composition of postharvest fruit. The graft copolymer treatment significantly reduced the incidence of gray mold caused by Botrytis cinerea in blueberries during storage (P < 0.05), and significantly stimulated the activity of key enzymes, including phenylalanine ammonia-lyase, chalcone isomerase, laccase, and polyphenol oxidase, leading to an increase in fungicidal compounds such as flavonoids, lignin, and total phenolics produced by the phenylpropanoid pathway in blueberries (P < 0.05). Moreover, the HC-g-SA coating altered bacterial and fungal community composition such that the abundance of postharvest fruit-peel pathogens was significantly reduced. After 8 days storage, the blueberry fruits treated by HC-g-SA had a weight loss rate of 12.42 ± 0.85 %. Therefore, the HC-g-SA graft copolymer had a positive impact on the control of gray mold in blueberry fruit during postharvest storage.

Natural Alkaloid Waltherione F-Derived Hydrazide Compounds Evaluated in an Agricultural Fungicidal Field.

In this project, quinoline and quinolone-containing hydrazide compounds were designed and synthesized by introducing a bioactive hydrazide group into the skeleton of waltherione F. The fungicidal activity revealed that some hydrazide compounds exhibited excellent and broad-spectrum fungicidal activity; especially, compounds E8, E12, and E16 showed more than 90% or even 100% inhibition rates against most pathogens at 50 μg·mL-1. The fungicidal mechanism indicated that compound E8 may affect the normal function of the plasma membrane, further generating changes in the morphology and subcellular structure of mycelia. Simultaneously, Fusarium graminearum may resist the E8-treated stress through the metabolic pathways related to l-glutamate, l-glutamine, and glutathione. Finally, the effect of compound E8 on wheat seedling's growth and the toxicity to zebrafish were accomplished. These results will provide important guidance to discover novel fungicidal lead compounds and explore new targets, which are effective ways to alleviate the increasingly severe drug resistance.

Research of Pesticide Metabolites in Human Brain Tumor Tissues by Chemometrics-Based Gas Chromatography-Mass Spectrometry Analysis for a Hypothetical Correlation between Pesticide Exposure and Risk Factor of Central Nervous System Tumors.

Pesticides are widely used, resulting in continuing human exposure with potential health impacts. Some exposures related to agricultural works have been associated with neurological disorders. Since the 2000s, the hypothesis of the role of pesticides in the occurrence of central nervous system (CNS) tumors has been better documented in the literature. However, the etiology of childhood brain cancers still remains largely unknown. The major objective of this work was to assess the potential role of pesticide exposure as a risk factor for CNS tumors based on questionnaires and statistical analysis of information collected from patients hospitalized in the Neurosurgery Department of the Habib Bourguiba Hospital Medium in Sfax, Tunisia, during the period from January 1, 2022, to May 31, 2023. It also aimed to develop a simple and rapid analytical method by the gas chromatography-mass spectrometry technique for the research traces of pesticide metabolites in some collected human brain tumor tissues in order to more emphasize our hypothesis for such a correlation between pesticide exposure and brain tumor development. Patients with a history of high-risk exposure were selected to conduct further analysis. Chemometric methods were adapted to discern intrinsic variation between pathological and control groups and ascertain effective separation with the identification of differentially expressed metabolites accountable for such variations. Three samples revealed traces of pesticide metabolites that were mostly detected at an early age. The histopathological diagnosis was medulloblastoma for a 10-year-old child and high-grade gliomas for 27- and 35-year-old adults. The bivariate analyses (odds ratio >1 and P value <5%) confirmed the great probability of developing cancer by an exposure case. The Cox proportional hazards model revealed the risk of carcinogenicity beyond the age of 50 as a long-term effect of pesticide toxicity. Our study supports the correlation between pesticide exposure and the risk of development of human brain tumors, suggesting that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased childhood brain tumor risk. This hypothesis was enhanced in identifying traces of metabolites from the carbamate insecticide class known for their neurotoxicity and others from pyridazinone, organochlorines (OCs), triazole fungicide, and N-nitroso compounds known for their carcinogenicity. The 2D-OXYBLOT analysis confirmed the neurotoxicity effect of insecticides to induce oxidative damage in CNS cells. Aldicarb was implicated in brain carcinogenicity confirmed by the identification of oxime metabolites in a stress degradation study. Revealing "aziridine" metabolites from the OC class may better emphasize the theory of detecting traces of pesticide metabolites at an early age. Overall, our findings lead to the recommendation of limiting the residential use of pesticides and the support of public health policies serving this objective that we need to be vigilant in the postmarketing surveillance of human health impacts.

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field.

Hydrazides are present in many bioactive molecules and exhibit a variety of biological activities, such as insecticidal, herbicidal, antifungal, antitumor, and antiviral effects. In this Review, we review the application of hydrazide and its derived structures in the agricultural fungicidal field, including monohydrazides, diacylhydrazines, hydrazide-hydrazones, and sulfonyl hydrazides. In addition, the antifungal mechanism of action of the hydrazide derivatives was analyzed and summarized, mainly involving succinate dehydrogenase inhibitors, laccase inhibitors, and targeting plasma membranes. Finally, based on the structural analysis of the novel fungicidal lead compounds, the structure-activity relationship of the hydrazide derivatives was constructed and the development trend of hydrazide structures in fungicidal applications was prospected. It is hoped that this Review can provide some significant guidance for the development of new hydrazide fungicides in the future.

Discovery of triphenylphosphonium (TPP)-conjugated N-(1,1'-biphenyl)-2-yl aliphatic amides as excellent fungicidal candidates.

Succinate dehydrogenase inhibitors (SDHIs) are the fastest growing agricultural fungicides at present, but their rapidly growing resistance is a serious problem for their application. Previously, we screened out a fungicidal lead compound CBUA-TPP (1) through triphenylphosphonium (TPP)-driven mitochondrial-targeting strategy. The targeting led to the rapid accumulation of 1 in mitochondria and the saturation inhibition of complex II in a short time, resulting in electron leakage and the explosion of reactive oxygen species (ROS). However, the contribution of biphenyl-2-amines to the activity of these compounds and their structure-activity relationship are still unknown. Two series of CBUA-TPP (1) analogues (series 2 and 3) were designed and synthesized. The bioassay results indicated that series 2 compounds generally showed much higher fungicidal activities than series 3, suggesting the crucial contribution of the biarylamine module in these targeted molecules and the pyridinyl substitution of phenyl is unfavorable to their activities. Interestingly, these two series of compounds displayed almost opposite substituent effects. Several compounds showed excellent fungicidal activities in vitro, among which compound 2-1 exhibited excellent field control efficacy on potato late blight. By optimizing the lead compound, the contribution of biarylamine in CBUA-TPP (1) analogs to the fungicidal activity is clarified. Several compounds, represented by 2-1, have great potential as fungicide candidates. They exhibit high and broad-spectrum fungicidal activities and are highly effective against common pathogenic fungi infecting vegetables and fruits both in vitro and field control. It not only provided a new choice for controlling these diseases, but its low resistance tendency also provided a better scheme for resistance management. © 2023 Society of Chemical Industry.

Effect of surfactants on the sorption-desorption, degradation, and transport of chlorothalonil and hydroxy-chlorothalonil in agricultural soils

The fungicide chlorothalonil (CTL) and its metabolite hydroxy chlorothalonil (OH-CTL) constitute a risk of soil and water contamination, highlighting the need to find suitable soil remediation methods for these compounds. Surfactants can promote the bioavailability of organic compounds for enhanced microbial degradation, but the performance depends on soil and surfactant properties, sorption-desorption equilibria of contaminants and surfactants, and possible adverse effects of surfactants on microorganisms. This study investigated the influence of five surfactants [e.g., Triton X-100 (TX-100), sodium dodecyl sulphate (SDS), hexadecyltrimethylammonium bromide (HDTMA), Aerosol 22 and Tween 80] on the sorption-desorption, degradation, and mobility of CTL and OH-CTL in two volcanic and one non-volcanic soil. Sorption and desorption of fungicides depended on the sorption of surfactants on soils, surfactants' capacity to neutralize the net negative charge of soils, surfactants’ critical micellar concentration, and pH of soils. HDTMA was strongly adsorbed on soils, which shifted the fungicide sorption equilibria by increasing the distribution coefficient (Kd) values. Contrarily, SDS and TX-100 lowered CTL and OH-CTL sorption on soils by decreasing the Kd values, which resulted in an efficient extraction of the fungicide compounds from soil. SDS increased the degradation of CTL, especially in the non-volcanic soil (DT50 values were 14 and 7 days in natural and amended soils, with final residues <7% of the initial dose), whereas TX-100 enabled an early start and sustenance of OH-CTL degradation in all soils. CTL and OH-CTL stimulated soil microbial activities without noticeable deleterious effects of the surfactants. SDS and TX-100 also reduced the vertical transport of OH-CTL in soils. Results of this study could be extended to soils in other regions of the world because the tested soils represent widely different physical, chemical, and biological properties.

Harnessing fungicide potential of hydrothermal liquefaction water from livestock manure: A new vision of integrated crop-livestock system

Hydrothermal liquefaction (HTL) can turn livestock manure into biocrude oil, but the aqueous phase (HTL-AP) attracts increasing concerns owing to its large amount and high toxicity. In this regard, a novel integrated crop-livestock system paradigm was proposed where HTL-AP from livestock manure was used as fungicide for phytopathogen control. To verify this strategy, Alternaria solani was employed as indicator phytopathogen, whereas cow manure (CM) and swine manure (SM) were used as the feedstock to obtain fungicide compounds via hydrothermal liquefaction (HTL). Results showed that the minimum inhibition concentration (MIC) of two HTL-APs was about 12%, where the main active compounds probably were phenols and nitrogenous compounds. The fungicide application would increase the manure carrying capacity by over 10%. Further observation revealed that HTL-AP exhibited inhibition through multiple pathways such as changing the mycelial morphology and cell membrane structure, resulting in metabolic disorders via impacting the generation of H2O2, ATP, reducing sugar and protein. The synergistic interaction among pathways was finally analyzed. Then, the effect of HTL-AP on seed-borne fungi control was evaluated via 36 groups of seed germination tests. For all that, this study provides new insights into the valorization of HTL-AP form livestock manure via unlocking its potential as sustainable fungicide constituents for phytopathogen control, further contributes to green development of current integrated crop-livestock system.