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A universal, green, and rapid lignin-based emulsive liquid-liquid microextraction (ELLME) method was established to detect nine triazole fungicides in water, juice, vinegar, and alcoholic beverages via UHPLC-MS/MS. By employing an environmentally friendly emulsifier (lignin), the proposed ELLME was compatible with more extractants, and not restricted to fatty acids. Due to the high amphiphilic properties and three-dimensional structure of lignin, the emulsion was quickly formed through several aspirate-dispense cycles of the green extractant (guaiacol) and lignin solution. And a micropipette was used for rapid microextraction. The limit of detection was 0.0002-0.0057 μg L -1 . The extraction recoveries and relative standard deviation were 81.7%-102.0% and 0.9%-7.1%, respectively. Finally, three green metric tools were used to verify the greenness of the whole procedure. The proposed lignin-based ELLME successfully emulsified green solvents, indicating that emerging solvents may be excellent alternatives as extractants in ELLME for pesticide residue analysis in food samples., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

It is highly desirable to develop a low-cost and rapid detection method for trace levels of carbendazim fungicide residues, which would be beneficial for improving human health and mitigating environmental issues. Herein, isolated single tungsten atoms were implanted onto well-organized metal-organic framework (MOF)-derived N-doped carbons to form W-N-C single-site heterojunctions with ultrahigh electrocatalytic activity. The coupling of W-N-C with Cu 3 (HHTP) 2 , an electronically conductive MOF with a large surface area and porous structure, exhibited enhanced electrocatalytic performance for the oxidation of carbendazim (CBZ) when they were used for decorating graphene nanoplatelet flexible electrode arrays fabricated via template-assisted scalable filtration. A wide linear range (3.0 nM-50 μM) with an ultra-low detection limit of 0.97 nM and fast response was achieved for CBZ analysis. Moreover, the sensing platform has been utilised to monitor CBZ levels in vegetable samples with satisfactory recovery rates of 97.2-102% and a low relative standard deviation of 1.9%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Using chemical fungicides is the main strategy for controlling potato late blight (PLB), a devastating pre- and postharvest disease caused by Phytophthora infestans , resulting in environmental pollution and health risks. It is of great importance to develop a biofungicide from microorganisms. Through isolating potato rhizosphere microorganisms, CQUSh011 was found to have antioomycete activity with strong inhibition on vegetative growth and virulence of P. infestans . Morphological and molecular identification indicated that CQUSh011 belongs to Streptomyces rapamycinicus . Based on genome, metabolome, and HPLC quantification, rapamycin and salicylic acid were found to be the two active metabolites against P. infestans . Continuous field trials showed that CQUSh011 has sustainable control efficiency against PLB, and the efficiency was better when combined with Infinito, along with an increased endophytic microbial community and biodiversity in potato roots. The results demonstrated the potential of CQUSh011 as a biofungicide against PLB and provided an alternative strategy for reducing the application of chemical fungicides.

Pathogenic microorganisms are a significant cause of food spoilage, adversely affecting both product quality and human health. This study evaluated the antifungal activities of 34 aldehydes against foodborne and plant pathogenic fungi, identifying 8 promising lead compounds. Among them, E , E -2, 4-nonadienal exhibited optimal effects against Rhizopus stolonifer with an EC 50 of 11.29 μg/mL. In vitro assays demonstrated that E , E -2, 4-nonadienal significantly impact R. stolonifer through both direct contact and fumigation. The preliminary mode of action (MOA) studies indicated that it effectively inhibited spore germination, disrupted ergosterol biosynthesis, and induced oxidative stress, affecting the permeability of the fungal cell membrane and altering mycelial morphology. Additionally, E , E -2, 4-nonadienal significantly reduced soft rot in spore-infected stored cherry tomatoes and showed low toxicity. Thus, aldehydes, exemplified by E , E -2, 4-nonadienal, are potential food and agricultural preservatives, offering efficiency, safety, and cost-effectiveness.

Fusarium head blight (FHB), caused by Fusarium graminearum , severely impacts global wheat production, reducing both the yield and quality. In China, fludioxonil, a phenylpyrrole fungicide, is used for managing FHB. This study assessed fludioxonil activity against 120 F. graminearum strains collected from Hubei, Zhejiang, and Jiangsu in 2024, revealing an average EC 50 value of 0.0273 ± 0.0062 μg/mL. We obtained two resistant mutants through chemical taming and discovered a novel point mutation of FgOs1-M460I. Site-directed mutagenesis confirmed that the FgOs1-M460I mutation greatly reduced fludioxonil sensitivity, with an EC 50 value greater than 100 μg/mL. These mutants also displayed reduced sexual and asexual reproduction and lower virulence and accumulated less glycerol under fludioxonil and osmotic stress compared to sensitive strain. The resistant mutants showed no cross-resistance with carbendazim, tebuconazole, phenamacril, pyraclostrobin, or pydiflumetofen. Thus, we conclude that the FgOs1-M460I substitution regulates fludioxonil resistance and plays a role in asexual reproduction, sexual reproduction, and pathogenicity.

Seed coating with fungicides is a common practice in controlling seed-borne diseases, but conventional methods often result in high toxicity to plants and soil. In this study, a nanoparticle formulation was successfully developed using the metal-organic framework UiO-66 as a carrier of the fungicide ipconazole (IPC), with a tannic acid (TA)-Zn II coating serving as a protective layer. The IPC@UiO-66-TA-Zn II nanoparticles provided a controlled release, triggered and regulated by environmental factors such as pH and temperature. This formulation efficiently controlled the proliferation of Fusarium fujikuroi spores, with high penetration into both rice roots and fungal mycelia. The product exhibited high antifungal activity, achieving control efficacy rates of 84.09% to 93.10%, low biotoxicity, and promoted rice growth. Compared to the IPC flowable suspension formula, IPC@UiO-66-TA-Zn II improved the physicochemical properties and enzymatic activities in soil. Importantly, it showed potential for mitigating damage to beneficial soil bacteria. This study provides a promising approach for managing plant diseases using nanoscale fungicides in seed treatment., Competing Interests: Declarations Ethics approval and consent to participate We confirmed that all methods involving the plant and its material adhered with the relevant institutional, national, and international guidelines and legislation. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In this study, S-methyl derivatives of dithiocarbamates (DTCs) were shown to significantly enhance chemiluminescence (CL) between Ce(IV) and efficient and environmentally friendly nitrogen-doped carbon dots (NCDs). Based on the elucidation of the CL mechanisms, an innovative approach involving high-performance liquid chromatography coupled with N-CDs and CL detection (HPLC-CDCL) was proposed. The developed method was successfully applied to the highly sensitive detection of three DTC fungicides (dimethyl dithiocarbamate, ethylene bisdithiocarbamate, and propylene bisdithiocarbamate) in tea. The recovery of the established method ranged 70.51-116.45%, with relative standard deviations (RSD) of <9.40%. The limit of detection (S/N = 3) was as low as 0.19 μg/L (as CS 2 ), which is superior to the previous methods and comparable to UPLC-tandem mass spectrometry (MS/MS). Moreover, the proposed approach does not require solid-phase extraction and offers excellent selectivity. This study proposes a novel method for the detection of DTCs in the food safety and environmental fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pathogenic fungi employ numerous strategies to colonize plants, infect them, reduce crop yield and quality, and cause significant losses in agricultural production. The increasing use of chemical pesticides has led to various ecological and environmental issues, including the emergence of resistant weeds, soil compaction, and water pollution, all negatively impacting agricultural sustainability. Additionally, the extensive development of synthetic fungicides has adverse effects on animal and human health, prompting the exploration of alternative approaches and green strategies for phytopathogen control. Microorganisms living in sponges represent a promising source of novel bioactive secondary metabolites, potentially useful in developing new nematicidal and antimicrobial agents. This study focuses on extracting bioactive compounds from endosymbiotic bacteria associated with the marine sponge Hyrtios erect sp. (collected from NIOF Station, Hurghada, Red Sea, Egypt) using various organic solvents. Bacillus sp. was isolated and identified through 16 S rRNA gene sequencing. The biocidal activity of Bacillus gotheilii MSB1 extracts was screened against plant pathogenic bacteria, fungi, and nematodes. The n-butanol extract showed significant potential as a biological fungicide against Alternaria alternata and Fusarium oxysporum. Both n-hexane and ethyl acetate extracts exhibited negative impacts against the plant pathogenic bacteria Erwinia carotovora and Ralstonia solanacearum, whereas the n-butanol extract had a positive effect. Regarding nematicidal activity, ethyl acetate and n-butanol extracts demonstrated in-vitro activity against the root-knot nematode Meloidogyne incognita, which causes serious vegetable crop diseases, but the n-hexane extract showed no positive effects. The findings suggest that bioactive compounds from endosymbiotic bacteria associated with marine sponges, particularly B. gotheilii MSB1, hold significant potential as alternative biological control agents against plant pathogens. The n-butanol extract, in particular, displayed promising biocidal activities against various plant pathogenic fungi, bacteria, and nematodes. These results support further exploration and development of such bioactive compounds as sustainable, environmentally friendly alternatives to synthetic pesticides and fungicides in agricultural practices., Competing Interests: Declarations Ethics approval and consent to participate The Faculty of Science, El-Menoufia University, Egypt, oversaw and sanctioned the sampling procedures for this experiment (Approval Code: MU08220231117). All methods and protocols employed adhered strictly to the Guide for the Care and Use of Agricultural Samples as stipulated by El-Menoufia University. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A series of myricetin derivatives containing diisopropanolamine were designed and synthesized. The in vitro inhibitory effects of the target compounds on 9 fungal pathogens and 3 bacterial pathogens were also evaluated. A12 had the best inhibitory effect against Xanthomonas oryzae pv. oryzae ( Xoo ), with an EC 50 value of 4.9 μg/mL, which was better than zinc-thiazole (ZT: EC 50 = 7.3 μg/mL) and thiodiazole-copper (TC: EC 50 = 65.5 μg/mL); A25 had the best inhibitory effect against Phomopsis sp . ( Ps ), with an EC 50 value of 17.2 μg/mL, which was better than azoxystrobin (Az: EC 50 = 22.3 μg/mL). In vivo inhibition tests were performed on kiwifruit for A25 and rice leaves for A12 . At 200 μg/mL, the curative activity of A12 against rice leaf blight was 40.7%, which was better than that of ZT (37.2%) and TC (32.9%), and the protective activity of A12 was 44.8%, which was better than that of ZT (39.5%) and TC (34.6%). The curative activity of A25 against kiwi soft rot disease was 70.1%, which was better than that of Az (62.8%). Preliminary elucidation of the possible mechanisms of action was carried out by experiments on fluorescence microscopy, scanning electron microscopy, formation of biofilms, density functional theory calculations, and so on.

As a continuation of our research on the pesticide development of Polygonum orientale L., the chemical constituents of the seeds of P. orientale were systematically investigated. Eleven natural compounds ( PO-1 to PO-11 ) were isolated from the EtOAc extract of P. orientale . Notably, compound PO-9 and its dimeric compound PO-10 were first isolated from P. orientale and possessed excellent acaricidal activity against Tetranychus cinnabarinus . With PO-9 and PO-10 as the lead compounds, two series of cinnamate derivatives were further synthesized, and their acaricidal, insecticidal, and fungicidal activities were evaluated systematically. The insecticidal activity results showed that dimeric derivative NKY-70 displayed the highest acaricidal activity against T. cinnabarinus and insecticidal activities against Brevicoryne brassicae and Myzus persicae . Furthermore, most of these compounds showed excellent in vitro antifungal activity against plant fungi. Compound NKY-66 displayed the highest and broad spectrum of antifungal activity against 23 fungi, and the respective EC 50 values were 0.09, 0.08, 0.12, 0.18, 0.12, and 0.09 mg/mL against Valsa mali , Fusarium oxysporum f. sp. cucumerinum, Fusarium graminearum , Magnaporthe oryzae , Colletotrichum capsici , and Phytophthora infestans , which were more potent than those of chlorothalonil and procymidone. Moreover, the in vivo fungicidal evaluation also demonstrated that compound NKY-66 could effectively control plant fungal diseases in the greenhouse and in the field, such as damping off, powdery mildew, and cucumber downy mildew. Therefore, these findings implied that the cinnamate derivative NKY-66 displayed superior in vitro and in vivo fungicidal activities and could be a potential candidate against plant fungal diseases.

The widespread use of chiral triazole fungicide cyproconazole (CPZ) in agricultural fields has led to frequent detection of CPZ in the environment. The restriction of CPZ in the EU raised wide concerns regarding its potential endocrine-disrupting effects (EDEs). The present study was conducted to evaluate EDEs of CPZ stereoisomers in vitro , in silico , and in vivo . The reporter gene assay indicated that all CPZ stereoisomers were agonists to the human estrogenic receptor α. (2 S ,3 S )-(+)- and (2 R ,3 S )-(-)-CPZ exhibited stronger binding capacities to ERα compared with (2 R ,3 R )-(-)- and (2 S ,3 R )-(+)-CPZ. Our computational studies showed consistent results with reporter gene assay, elucidating the stereoselective binding mode of CPZ to estrogen receptor. In zebrafish embryos, the 96h-lethality of CPZ stereoisomers ordered (2 R ,3 R )-(-)- > (2 R ,3 S )-(-)- > (2 S ,3 S )-(+)- > Rac- > (2 S ,3 R )-(+)-CPZ. Stereoselective developmental toxicity of CPZ was observed while (2 R ,3 S )-(-)-CPZ is the most toxic isomer. The estrogenic hormones were significantly decreased in (2 S ,3 R )-(+)- and (2 R ,3 S )-(-)-CPZ groups and enhanced in (2 S ,3 S )-(+)- and (2 R ,3 R )-(-)-CPZ, along with the gene expression in hypothalamic-pituitary-gonad axis altered. CPZ shows no thyroid hormone activity. These data clarified that CPZ is a new-found endocrine disruptor threatening human health and each stereoisomer of CPZ showed stereoselective EDEs by regulating the nuclear receptor-mediated gene expression.

Peanut root rot (PRR) is a prevalent and destructive plant disease attributed to Fusarium solani . Pydiflumetofen (Pyd) is a succinate dehydrogenase inhibitor (SDHI) with antifungal activity against F. solani , yet its resistance mechanism has been inadequately explored. In this study, the EC 50 values for Pyd against 93 F. solani strains ranged from 0.0095 to 0.3815 μg/mL, with all strains displaying a minimal inhibitory concentration (MIC) of ≤1 μg/mL. Four Pyd-resistant (PR) mutants were obtained, exhibiting stable resistance levels and comparable fitness to their parental strains in terms of mycelia growth, hyphal tip morphology, asexual reproduction, and virulence assessment. Five-point mutations, including FsSdhC1 A82V , FsSdhC2 L76M , FsSdhC2 L135V , FsSdhC2 F137L , and FsSdhC2 F147L , were identified in the PR mutants. However, molecular docking analysis indicated that only FsSdhC1 A82V and FsSdhC2 L135V could influence the sensitivity of F. solani to Pyd. These findings help evaluate F. solani 's resistance to Pyd and guide future PRR management with this fungicide.

The development of novel, safe, and efficient pest and disease control technologies for agricultural crops remains a pivotal area of research. In this study, by combining ZIF-8 and ZIF-90, a water-stable, pH-responsive bilayer MOF nanoparticle (NP) named Z8@Z90 was created, and tebuconazole (TEB) was added to form T@Z8@Z90, used for controlling peanut southern blight. The loading efficiency of TEB within the T@Z8@Z90 reached 26.15%, enabling rapid release in acidic environments triggered by oxalic acid (OA) secreted by Sclerotium rolfsii . In vitro experiments showed that T@Z8@Z90 can regulate the oxalic acid secretion of S. rolfsii and destroy its cell membrane structure. Additional experiments revealed that T@Z8@Z90 reduced sclerotial formation, decreased the total protein content of sclerotia, and influenced their sensitivity to pesticides, thereby mitigating the risk of reinfection by S. rolfsii . Notably, T@Z8@Z90 exhibited efficient translocation within peanut seedlings, being absorbed through the roots and transported to the leaves. At a concentration of 200 mg/L, T@Z8@Z90 exhibited high safety profiles for peanut seedling growth compared to the TEB suspension. Moreover, T@Z8@Z90 is safer for earthworms than TEB SC. Overall, this study offers valuable insights for the management of soil-borne diseases in agriculture and contributes to the advancement of sustainable agricultural practices.

Streptomyces species can form beneficial relationships with hosts as endophytes, including the phytopathogen-inhibiting strain, Streptomyces griseoaurantiacus MH191, isolated from wheat plants. Using genomic characterization and untargeted metabolomics, we explored the capacity of strain MH191 to inhibit a range of fungal phytopathogens through the production of secondary metabolites. Complete genome assembly of strain MH191 predicted 24 biosynthetic gene clusters. Secondary metabolite production was assessed following culture on six different media, with the detection of 205 putative compounds. Members of the manumycin family, undecylprodigiosin, and desferrioxamine were identified as the predominant metabolites. Antifungal activity was validated for undecylprodigiosin and manumycin. These compounds were produced from different BGCs, which showed similarity to asukamycin, undecylprodigiosin, and FW0622 gene clusters, respectively. The growth of strain MH191 on different media illustrated the metabolic regulation of these gene clusters and the strain's extended chemical potential, with the asukamycin gene cluster alone, producing a variety of antifungal metabolites. The study highlights the extended chemical capability of strain MH191, which could be exploited as a biological control agent for designing future crop protection solutions.

Azo-incorporating was reported to be an effective strategy for increasing SDH inhibitory activity but for poor in vivo control effects. Herein, the azo-incorporated compounds were structurally optimized to retain a preferential conformation by replacing the azo bond with their bioisosteres. Interestingly, the 1,2,4-oxadiazole compound D2 displayed a broad fungicidal spectrum as well as fluxapyroxad. More excitedly, compound D2 showed excellent antifungal activities against rice sheath blight disease both in vitro (EC 50 = 0.001 μg/mL) and in vivo (EC 50 = 1.08 μg/mL, EC 95 = 4.67 μg/mL). In addition, an extra π-π interaction was found between the 1,2,4-oxadiazole ring of compound D2 and the phenyl ring of residue D&#95;Y586, which might interpret the enhanced potency of compound D2 against Rhizoctonia solani . Further structural optimizations of the 1,2,4-oxadiazole compounds gave several analogues that made a breakthrough in controlling rice blast disease. These 1,2,4-oxadiazole compounds, derived from azobenzene derivatives, could be antifungal leads especially against R. solani and Magnaporthe grisea , exemplifying an interesting mode of pesticide discovery and providing theoretical guidance for innovation of the SDHI fungicide.

In the current study, a new magnetic sorbent (Fe 3 O 4 @2,6-diamino-4-(3,4-dihydroxyphenyl) pyridine-3,5-dicarbonitrile) was prepared as a new and efficient sorbent to be used in the magnetic solid-phase extraction method to extract tebuconazole and propiconazole as model compounds. In this regard, effective parameters such as pH of the sample solution, desorption volume, ionic strength, extraction time, desorption time, and amount of the magnetic sorbent were optimized using experimental design. In the optimal condition, the linear dynamic ranges for tebuconazole and propiconazole were between 0.5 and 200.0 µg/L. Also, the limits of detection, limits of quantification, and relative standard deviations were 0.21-0.14 µg/L, 0.49-0.45 µg/L, and 1.3%-4.6%, respectively. The estimated enrichment factors for tebuconazole and propiconazole were 22 and 28, respectively. The absolute recovery (AR%) values for tebuconazole and propiconazole were also 67% and 84%, respectively. Finally, the proposed method was used for determination of tebuconazole and propiconazole in cucumber, tomato, orange, and lemon fruits. The obtained result confirmed that the presented method is capable for the analysis of the selected analytes in complicated matrices. In addition, the ARs% were in the range of 67%-84%. The result proved that the presented method can be an alternative to the extraction process of various pesticides., (© 2024 Wiley‐VCH GmbH.)

Existing cleaning methods mainly focus on removing free-state pesticides. However, mancozeb can bind to the wax layer of grapes, forming bound-state residues that are difficult to remove. This study aims to develop an effective cleaning strategy to eliminate both free and bound mancozeb residues from grapes. Compared with the untreated mancozeb aqueous solution, the concentration of free mancozeb significantly decreased (p < 0.05) after treatment with ozonated water (OW), electrolyzed water (EW), and their combination (OW+EW) for 60 min. The combined treatment synergistically promoted mancozeb degradation, thus reducing its half-life to 38% and 75% of that observed when OW and EW were used alone, respectively. To investigate the effect of the waxy layer on mancozeb removal, oleanolic acid (OLA) was selected as a representative component. The binding effect of OLA limited the degradation of mancozeb in OW and EW, extending its half-life by 1.27 and 1.20 times, respectively. Density functional theory elucidated the mechanism by which the binding of OLA affects the degradation of mancozeb. Interestingly, the decomposition of mancozeb in OW + EW was almost unaffected by the introduction of OLA, indicating that the combined treatment could effectively remove bound-state mancozeb. The combined treatment was then successfully applied to remove mancozeb from grapes. After exposure to OW + EW for 10 min, the removal efficiency of mancozeb reached up to 80.61% with minimal risks of ethylene thiourea formation. There was no obvious change in the surface color of grapes after treatment. The findings provide valuable guidance for removing mancozeb from fresh fruits rich in waxy coatings., (© 2024 Institute of Food Technologists.)

Multiscale particle size functional pesticide carriers can provide more efficient protection for plants, but this protection is difficult to achieve via single-scale formulation technology. This study presents a novel one-step method for the preparation of lignin-based micro/nanocapsules with controllable proportions within a unified system. This strategy enables the adjustment of the proportion of nanocapsules to between 18.81% and 85.21%. The microcapsules (MCs) vary in diameter from 2 to 3 µm, whereas the nanocapsules (NCs) span from 160 to 220 nm, with an encapsulation efficiency exceeding 90%. An increased proportion of NCs in the system leads to faster release, heightened sensitivity to UV light, and enhanced penetration into the leaves. During Phytophthora capsici (P. capsici) infection, the NCs in the leaves interact with the defensive enzymes of the plant to quickly respond. Moreover, an optimal balance of MCs and NCs is key to effective fungicide use, not just a higher concentration of NCs. A 65:35 ratio of NCs to MCs ensures effective inhibition of P. capsici outside leaves and a rapid response to leaf invasion. This study enhances fungicide efficiency and advances the development of nanoresponsive fungicides to promote sustainable agricultural practices., (© 2024 Wiley‐VCH GmbH.)

Background: Utilizing fungicides to protect crops from diseases is an effective method, and novel eco-friendly plant-derived fungicides with high efficiency and low toxicity are urgent requirements for sustainable crop protection., Result: Two series of rosin-based fungicides (totally 35) were designed and synthesized. In vitro fungicidal activity revealed that Compound 6a (Co. 6a) effectively inhibited the growth of Valsa mali [median effective concentration (EC 50 ) = 0.627 μg mL -1 ], and in vivo fungicidal activity suggested a significant protective efficacy of Co. 6a in protecting both apple branches (35.12% to 75.20%) and apples (75.86% to 90.82%). Quantum chemical calculations (via density functional theory) results indicated that the primary active site of Co. 6a lies in its amide structure. Mycelial morphology and physiology were investigated to elucidate the mode-of-action of Co. 6a, and suggested that Co. 6a produced significant cell membrane damage, accelerated electrolyte leakage, decreased succinate dehydrogenase (SDH) protein activity, and impaired physiological and biochemical functions, culminating in mycelial mortality. Molecular docking analysis revealed a robust binding energy (ΔE = -7.29 kcal mol -1 ) between Co. 6a and SDH. Subsequently, biosafety evaluations confirmed the environmentally-friendly nature of Co. 6a via the zebrafish model, yet toxicological results indicated that Co. 6a at median lethal concentration [LC 50(96) ] damaged the gills, liver and intestines of zebrafish., Conclusion: The above research offers a theoretical foundation for exploiting eco-friendly rosin-based fungicidal candidates in sustainable crop protection. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Synergistic effect of dimethomorph (DIM) and pyrimethanil (PYM) was evaluated using the Wadley method and the molecular mechanism of the antifungal effects of the combined treatment was systematically investigated. DIM+PYM had a synergistic effect on Phytophthora capsici, with the synergistic effect being observed at 5:1, at which the synergy coefficient was 1.8536. The mycelia of the pathogen treated with DIM+PYM were branched, uneven in thickness, and swollen. Moreover, scanning electron microscopy (SEM) revealed that DIM+PYM caused mycelium breaks, swelling, and apex enlargement, while transmission electron microscopy (TEM) revealed structural damage, cavities, and cell membrane morphological abnormalities. DIM+PYM inhibited the growth of mycelia, destroyed the cell membrane, interfered with energy metabolism, reduced protein and sugar content. Additionally, the transcriptome and metabolome of fungi treated with DIM+PYM changed significantly; specifically, there were 1571 differentially expressed genes and 802 differential metabolites. DIM+PYM may mainly damage the cell membrane, energy, protein, soluble sugar pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The natural product paeonol is a rich and sustainable natural bioresource, and its derivatives have various unique biological efficacy. As is well known, Schiff bases are a class of organic compounds with a wide range of biological activities, including anti-fungal, insecticidal, anti-viral, and nematicidal., Results: To discover biorational natural product-based pesticides, nine intermediates (2-10), 12 sulfonylhydrazones (11a-11c, 12a-12c, 13a-13c, and 14a-14c) and 20 benzylidene hydrazones (18a-18r, 19a, and 20a) were synthesized by structural modification of paeonol, and their structures were characterized by proton nuclear magnetic resonance ( 1 H NMR), carbon-13 ( 13 C) NMR, and high-resolution mass spectrometry (HRMS). The stereochemical configurations of compounds 14a, 18d, and 18r were unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, bioactivities of these compounds as anti-oomycete, anti-fungal, and nematicidal agents against three serious agricultural pests, Phytophthora capsici, Fusarium graminearum, and Heterodera glycines were evaluated. Among all tested compounds: (i) compound 7 exhibited promising anti-oomycete against Phytophthora capsici, with a half maximal effective concentration (EC 50 ) value of 15.81 mg L -1 ; (ii) compounds 2, 7, 10, and 19a displayed promising anti-fungal against F. graminearum, with EC 50 values of 12.22, 14.72, 23.39, and 33.10 mg L -1 , respectively; (iii) ten compounds (12a-12c, 14c, 18g-18j, 18m, and 19a) showed significant nematicidal activity against H. glycines, with median lethal concentration (LC 50 ) values all less than 30.00 mg L -1 . Especially for compound 18g, its LC 50 value is the smallest, at 12.65 mg L -1 ., Conclusion: The research results indicate that introducing nitro groups at the C5 position of paeonol, or introducing halogens at both C5 and C3 positions, can significantly enhance its biological activity against Phytophthora capsici, F. graminearum, and H. glycines. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

In this study, 12 pairs of tautomeric flavonol derivatives containing quinoxaline were synthesized. The results of antifungal activity showed that in the enol-keto tautomerism, the target compounds containing keto ( Y B series) had better inhibitory activity against Sclerotinia sclerotiorum ( S.s .) than compounds containing enol ( Y A series). Y B9 showed the strongest antifungal activity against S.s., and the median effective concentration (EC 50 ) value was 1.0 μg/mL, which was better than azoxystrobin ( Az , 35.3 μg/mL). In vivo fungal inhibition experiments showed that the protective activity of Y B9 against rape leaves was 83.4% at 200 μg/mL, which was superior to that of Az (70.2%). The activity of succinate dehydrogenase and molecular docking results showed that Y B9 had a stronger antifungal effect than Y A9 . The results of oxalic acid content determination showed that Y B9 could reduce the pathogenic ability of S.s. Then, the inhibitory effect of Y B9 against S.s. was further verified by scanning electron microscopy, fluorescence microscopy, cell membrane permeability, cell content leakage, and malondialdehyde content.

Plant pathogenic fungi pose a substantial challenge to agricultural production, but the conventional fungicide-based approaches are losing importance. As agents with broad-spectrum antibacterial effects, gold nanoparticles (Au NPs) are found to have antifungal effects; however, no study has examined their application in agriculture as fungicides. Accordingly, this study investigates the activity of 2-mercaptoimidazole-capped Au NPs (MI-Au NPs) against the 'top' plant pathogenic fungi, finding that they could inhibit Magnaporthe oryzae , Botrytis cinerea , Fusarium pseudograminearum and Colletotrichum destructivum by inducing cytoplasmic leakage. Moreover, MI-Au NPs are found to protect plants from infection by B. cinerea . Specifically, pot experiments demonstrate that MI-Au NPs decrease the incidence rate of B. cinerea infection in Arabidopsis thaliana from 74.6% to 6.2% and in Solanum lycopersicum from 100% to 10.9%, outperforming those achieved by imazalil. Furthermore, the biosafety assays reveal that MI-Au NPs cannot penetrate the cuticle of plant cells or negatively influence plant growth, and it is safe to mammalian cells. In summary, the findings of this study will support the development of NP-based antifungal agents for use in agriculture.

To develop novel succinate dehydrogenase (SDH) inhibitors for sustainable crop protection, a series of dehydroabietyl-diamide-based fungicides (a total of 21) were designed. In vitro fungicidal activity measurement showed that compound 3u exhibited excellent fungicidal activity against Valsa mali (half-maximal effective concentration, EC 50 = 0.195 μg/mL), surpassing that of the positive control carbendazim (EC 50 = 1.35 μg/mL). The in vivo fungicidal activity assessment suggested that 3u exhibited a protective effect on apple branches (69.7-48.1%) and apples (94.6-56.6%). Furthermore, biosafety evaluation indicated that 3u was significantly environmentally friendly toward zebrafish. Subsequently, morphology, physiology, and molecular docking were investigated to elucidate the mode of action of 3u against V. mali . Results demonstrated a strong binding between 3u and SDH, resulting in decreased SDH activity (half-maximal inhibitory concentration, IC 50 = 11.7 μg/mL). Moreover, 3u disrupted the mycelial cell membrane and accelerated electrolyte leakage, ultimately resulting in the death of V. mali . These findings suggest that 3u could serve as a potent SDH inhibitor for sustainable crop protection.

Phytophthora infestans -induced potato late blight is considered the "cancer of the potato crop." In this work, mesoporous silica nanoparticles (MSNs) with ultrahigh specific surface area (786.28 m 2 /g) were synthesized, which significantly inhibited P. infestans compared with some commercial fungicides. Moreover, MSNs inhibited the growth and reproductive of P. infestans processes, including germination, sporangia infection, and zoospore release. MSNs targeted key biological pathways and induced a stress response in the P. infestans , leading to reactive oxygen species (•O 2- , •OH, and 1 O 2 ) production and structural damage of sporangia. Pot experiments showed that MSNs are translocated from leaves to roots of potato plants, enhancing physiological and biochemical processes, alleviating drought stress, improving resistance to pathogens, and exhibiting soil microbe-friendly. This study systematically reveals the mechanism of MSNs to weaken the reproduction process of P. infestans and confirm the safety and feasibility of MSNs as a green and sustainable fungicide.

Pesticides, including fungicides, are one of the important groups of environmental toxins that affect human and animal health. Studies have shown that these compounds are considered chemical pollutants. Carbendazim is a systemic fungicide. Unfortunately, excessive use of carbendazim has caused environmental pollution all over the world. In this study, the effect of carbendazim on the enzyme elastase (secreted from the endocrine gland of the pancreas) has been investigated. In a study, the performance and reaction of carbendazim with elastase were investigated using spectroscopic techniques. The stability and structure of elastase enzymes were studied under the influence of carbendazim. The results of fluorescence emission and UV-visible absorption spectrum showed that in the presence of carbendazim, there is an increase in UV-Vis absorption and a decrease in the intensity of the intrinsic fluorescence emission in the protein spectrum. Additionally, a decrease in the thermal stability of elastase was observed in the presence of carbendazim. The stability and structure of elastase enzyme were investigated in the presence of carbendazim. The results revealed that the UV-Vis absorption increased due to the presence of carbendazim, as indicated by the hyperchromic spectrum at 220 and 280 nm peaks. Additionally, the intrinsic fluorescence emission in the protein spectrum decreased with increasing carbendazim concentration at three different temperatures (298, 303, and 313 K). Moreover, the study demonstrated that the TM decreased from 2.59 to 4.58 with the increase of carbendazim, suggesting a decrease in the stability of the elastase structure in response to the elevated carbendazim concentration. According to the results of the research, the interaction between elastase and carbendazim has occurred, and changes have been made in the enzyme under the influence of carbendazim. The formation of the complex between elastase and carbendazim was consistent with the results obtained from molecular simulation and confirmed the thermodynamic data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

To develop further novel environmentally friendly antifungal agents with high efficacy, a series of pyrazole-5-sulfonamide derivatives were designed and synthesized by using the active molecules synthesized in previous works as lead compounds. Their antifungal activities were evaluated in vitro against ten highly destructive plant pathogenic fungi. The bioassay results indicated that more than half of the target compounds displayed potent antifungal activities (inhibition rate ≥85%) against Valsa mali and Sclerotinia sclerotiorum at 20 mg/L. Among them, compound C22 exhibited significant broad-spectrum antifungal activities against V. mali , S. sclerotiorum , Rhizoctonia solani , Botrytis cinerea , and Trichoderma viride , with EC 50 values of 0.45, 0.49, 3.06, 0.57, and 1.43 mg/L, respectively. Moreover, compounds C21 and C22 exhibited remarkable protective effects on apple Valsa canker similar to tebuconazole (89.5%) at 50 mg/L. Preliminary antifungal mechanism investigations demonstrated that compound C22 may have inhibited V. mali mycelial growth by inducing oxidative damage to the mycelium and compromising the integrity of the cell membrane. Meanwhile, compounds C21 and C22 exhibited no obvious toxicity to worker bees ( Apis mellifera ligustica). Taken together, these pyrazole-5-sulfonamide derivatives, particularly compound C22 , possess huge potential to be developed as novel environmentally friendly fungicides with high efficacy.

Isopyrazam (IPZ) is a new chiral fungicide. For bioactivity, there was a 3.37-1578 times difference among the four stereoisomers. For Alternaria alternata and Phoma multirostrata , cis -(1 S ,4 R ,9 S ) - IPZ had the greatest activity. Using cis -IPZ might improve the efficacy and reduce the dosage of the racemate by 54.7-72.2% for A. alternata and P. multirostrata . To zebrafish, trans -IPZ showed the highest acute toxicity (LC 50 , 0.096 mg/L). The degradation half-lives of IPZ stereoisomers in the five crops ranged from 3.50 to 15.2 days. Cis -IPZ was preferentially degraded in grape, pear, and celery. The residual concentrations of IPZ in grape and celery were still higher than the maximum residue limit, and the acute and chronic dietary intake risks of IPZ in celery were unacceptable (RQ a : 146-250%, HQ: 117-200%), which were worthy of further researching. Based on the research results, it is safer and more reasonable to use IPZ in the form of a racemate with a high ratio of cis -IPZ.

To discover novel inhibitors of the complex I reduced nicotinamide adenine dinucleotide (NADH) oxidoreductase as fungicides, a series of 6-isothiazol-5-ylpyrimidin-4-amine-containing compounds were designed using a computer-aided pesticide design method and splicing of substructures from diflumetorim and isotianil. In vitro fungicidal bioassays indicated that compounds T17 - T24 showed high inhibitory activity against Rhizoctonia solani with an effective concentration (EC 50 ) value falling between 2.20 and 23.85 μg/mL, which were more active than or equivalent to the lead diflumetorim with its EC 50 of 19.80 μg/mL. In vivo antifungal bioassays demonstrated that, at a concentration of 200 μg/mL, T7 and T21 showed higher inhibition against Pseudoperonospora cubensis than all other compounds, while T23 exhibited the highest inhibition against Sphaerotheca fuliginea . T23 showed an approximately twofold lower inhibition potency against R. solani complex I NADH oxidoreductase than diflumetorim. Molecular docking and transcriptomic analyses indicated that T23 and diflumetorim both might share the same mode of action, targeting NADH oxidoreductase. T23 as a good fungicidal candidate against R. solani is worthy of further investigation.

As part of continuous work to explore novel and efficient fungicides originating from natural products, a series of cyclobutyl oxime ester derivatives containing an α,β-unsaturated carbonyl moiety were designed and synthesized. In line with the primary evaluation of the inhibitory effect on common pathogenic fungi causing crop failure, a systematic study on the antifungal activity of target compounds against Rhizoctonia solani was carried out. Most target compounds exhibited satisfactory antifungal activity, and 10 of them were superior to the positive control trifloxystrobin. The most notable median effective concentration (EC 50 ) of compound 6b was 1.70 μg/mL, which was considerable for an intensive study. The control efficacy of compound 6b on potted rice against R. solani was superior to trifloxystrobin at identical concentration. The mycelial morphology and cell membrane permeability of the treated fungi were disrupted, and the meaningful enzyme activities of SDH and POD were also restrained. The reactive oxygen species, nuclear morphology, and mitochondrial membrane potential of the treated hypha reflected an apparent difference compared with the normal morphology, which represented mitochondrial function damage. In addition, chemical features essential for the activity and docking mode within the compound and cytochrome bc 1 complex were accessed by computer-aided technology. This study provided insights into the development of new green and efficient fungicides targeting the mitochondria.

The discovery of natural product-derived novel nanopesticide systems can effectively address the adverse effects caused by the improper use of traditional fungicides. In this research, 33 novel 3-carene-derived amide-thiourea derivatives 5a - 5zg were designed using laccase as the biological target, synthesized from natural renewable forest biomass resource 3-carene as the starting material, and structurally confirmed by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, high-resolution mass spectrometry, and single crystal X-ray diffraction. The antifungal activity of the target compounds against eight plant pathogenic fungi was evaluated, and the results presented that target compound 5g exhibited excellent and broad-spectrum antifungal activity against the eight tested phytopathogenic fungi. Furthermore, the important contribution of the gem -dimethylcyclopropane structure in the antifungal activity of compound 5g was revealed through two negative controls without the gem -dimethylcyclopropane structure. Besides, compound 5g also demonstrated a prominent laccase inhibitory activity. The fluorescence quenching of the laccase with compound 5g , the chelating characteristics of compound 5g , and the interaction mode between the laccase and compound 5g presented that the target compound 5g probably exhibited excellent antifungal activity by acting on the laccase target. Cytotoxicity assay revealed that compound 5g had a low cytotoxicity for LO2 and HEK293T cell lines. On the other hand, to further improve the application potential of compound 5g , the 3-carene molecular skeleton containing gem -dimethylcyclopropane ring was grafted onto chitosan, and two nanopesticide carriers CACS and CATCS with sustained releasing performance were synthesized for loading compound 5g . 3-Carene-derived nanochitosan carrier CATCS showed a relatively regular, loose, and porous reticular structure, which displayed high dispersibility and good thermostability. In addition, this carrier had a higher drug-loading capacity and sustained releasing performance than that of the unmodified chitosan. This research identified that the target compound 5g could be used as a promising lead compound for fungicide against the laccase target, meanwhile, the complex 5g /CATCS deserved further study as a nanopesticide candidate.

Penicillium expansum is the major fungus that causes blue mold and produces patulin, threatening human health. Due to health and environmental pollution concerns, chitosan (CS) has attracted more and more attention as a safer alternative to synthetic fungicides for the control of blue mold. In the present study, four different benzimidazole groups were introduced onto CS by the acylation reaction to obtain benzimidazole-based chitosan derivatives (R1b-R4b). After being well-characterized with Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-vis spectra), and nuclear magnetic resonance (NMR), their antifungal activities against P. expansum were screened. Results showed that the inhibitory effects of chitosan derivatives against the pathogen were significantly correlated with chitosan derivatives' concentration and their structures. R4b was shown as optimum with good solubility and antifungal activity with a minimum inhibitory concentration (MIC) value of 0.5 mg/mL and a minimum fungicidal concentration (MFC) value of 2.0 mg/mL. The remarkable antifungal efficiency of R4b against P. expansum was further demonstrated in terms of spore germination, mycelial growth, patulin production, and the preliminary antifungal mechanism. R4b exhibited significant inhibition of patulin production, while its antifungal mechanism was revealed by destroying cell membrane integrity and inducing membrane depolarization. Furthermore, R4b treatment could significantly reduce the incidence of blue mold rot in apple fruit, and the MTT assay showed the nontoxicity of R4b against Raw 264.7, HBZY-1, and Caco-2 cells. Altogether, these results indicate that it is promising to be used as a fruit preservative in the future.

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.

Flutriafol, a globally utilized triazole fungicide in agriculture, is typically applied as a racemic mixture, but its enantiomers differ in bioactivity and environmental impact. The synthesis of flutriafol enantiomers is critically dependent on chiral precursors: 2,2-bisaryl-substituted oxirane [(2-fluorophenyl)-2-(4-fluorophenyl)oxirane, 1a ] and 1,2-diol [1-(2-fluorophenyl)-1-(4-fluorophenyl)ethane-1,2-diol, 1b ]. Here, we engineered a Rhodotorula paludigensis epoxide hydrolase ( Rp EH), obtaining mutant Escherichia coli / Rpeh H336W/L360F with a 6.4-fold enhanced enantiomeric ratio ( E ) from 5.5 to 35.4. This enabled a gram-scale resolution of rac - 1a by E. coli / Rpeh H336W/L360F , producing ( S )- 1a (98.2% ee s ) and ( R )- 1b (75.0% ee p ) with 44.3 and 55.7% analytical yields, respectively. As follows, chiral ( S )-flutriafol (98.2% ee ) and ( R )-flutriafol (75.0% ee ) were easily synthesized by a one-step chemocatalytic process from ( S )- 1a and a two-step chemocatalytic process from ( R )- 1b , respectively. This chemoenzymatic approach offers a superior alternative for the asymmetric synthesis of flutriafol enantiomers. Furthermore, molecular dynamics simulations revealed insight into the enantioselectivity improvement of Rp EH toward bulky 2,2-bisaryl-substituted oxirane 1a .

Alternaria alternata is a common plant pathogen that can infect crops and reduce their production. In this work, an antagonism experiment between A. alternata and the essential oil of arborvitae ( Platycladus orientalis ) was performed, and it was proven that A. alternata had developed resistance to this plant-derived fungicide. A. alternata facilitated the biotransformation of hinokitiol ( 1 ), the main antifungal compound in the essential oil of arborvitae, into ( R )-2-hydroxy-β-methylbenzeneethanol ( 2 ), which does not have antifungal activity against A. alternata . This biotransformation is an unusual ring-contraction reaction that was verified to be catalyzed by P450 enzyme hydroxylation and Baeyer-Villiger oxidation. In addition, the P450 enzyme inhibitors 1-aminobenzotriazole and piperonyl butoxide effectively prevented the destruction of the hinokitiol structure by A. alternata , and the combined use of these P450 enzyme inhibitors significantly increased the antifungal activity of hinokitiol. This work provides a theoretical reference for the further development of botanical fungicides.

Fungal secondary metabolites play a highly significant role in crop protection, which is related to their antifungal activity against agriculturally important phytopathogens. In fact, plant diseases caused by fungi including species belonging to the genera of Alternaria , Botrytis , and Fusarium have become increasingly serious affecting crop yield and quality. Hence, there is increasing awareness by the scientific community of the importance of exploiting fungal products for finding new compounds able to inhibit phytopathogens. In this study several drimane-type sesquiterpenes have been detected for the first time as products of Aspergillus xerophilus by GC-MS analysis of the organic extracts obtained from the mycelia and culture filtrates of the fungus grown on two different substrates. Seven pure drimane-type sesquiterpenes were also isolated and identified by spectroscopic methods. The inhibitory effects of the pure compounds have been investigated against three phytopathogenic fungi of agrarian crops (i.e., Botrytis cinerea , Alternaria alternata , and Fusarium oxysporum f. sp. pisi ). Among the drimane-type sesquiterpenes isolated in this study, 9,11-dihydroxy-6-oxodrim-7-ene is the most active against the three phytopathogens. Our findings also reveal the high sensitivity of A. alternata to the isolated compounds. These results pave the way for future applications in agriculture of both A. xerophilus and its metabolites.

Two endophytes from the same Ginkgo biloba host were isolated and cultured separately. Three new eremophilane sesquiterpenoids ( 1-3 ), three new furan derivates ( 6 , 8 - 9 ), one new polyketide ( 10 ), and four known compounds ( 4 , 5 , 7 , 11 ) from Paraphaeosphaeria sp. and two new 10-membered macrolides ( 12 - 13 ), a new liner polyketide ( 14 ), a new benzofuran ( 15 ), and six known compounds ( 16 - 21 ) from Nigrospora oryzae were isolated. The structures of the isolated compounds were determined by spectroscopic methods, NMR calculations, and ECD calculations. The compounds 3 - 7 , 9 - 10 , 12 , and 14 - 17 showed significant antiphytopathogenic effects against mycotoxigenic Alternaria sp. comparable to the activity of nystatin (positive control). Compounds 2 , 6 , 8 , 9 , and 18 indicated inhibitions against phytopathogen Fusarium asiaticum with MICs < 10 μg/mL. In addition, the compounds with weak antifungal activities from two endophytes were mixed to test their antifungal activity. The results showed that the metabolites from two endophytes had synergistic antifungal effects, and the beneficial interactions between natural products can induce more antifungal effects against plant pathogens than that of single compounds.

Based on previous research, this study synthesized 24 compounds by splicing the substructures of the indolyl group and the isothiocyanate group. Alternaria alternata , Phytophthora capsici , Botrytis cinerea, and Valsa mali were used to test the activity of the target compounds. At 100 μg/mL, compounds 8 , 13 , 14 , and 17 exhibited excellent inhibitory effects of more than 80% on P. capsici , B. cinerea, and V. mail . The EC 50 values of compounds 13 and 14 were 0.64 and 2.08 μg/mL, respectively. Potted antifungal activity demonstrated that compounds 13 and 14 had a protective effect of around 80% against B. cinerea at 200 μg/mL. Further physiological and biochemical studies on B. cinerea revealed that compound 13 thickened cell walls and caused mitochondrial vacuolization. Moreover, theoretical calculations indicated that the charge distribution of indolyl isothiocyanate compounds played a crucial role in the observed fungicidal activity. In summary, this study provided fundamental reference data for the derivative synthesis of these indolyl isothiocyanate compounds.

Plant pathogenic fungi frequently disrupt the normal physiological and biochemical functions of plants, leading to diseases, compromising plant health, and ultimately reducing crop yield. This study aimed to address this challenge by identifying antifungal agents with innovative structures and novel mechanisms of action. We designed and synthesized a series of flavonoid derivatives substituted with 5-sulfonyl-1,3,4-thiadiazole and evaluated their antifungal activity against five phytopathogenic fungi. Most flavonoid derivatives demonstrated excellent antifungal activity against Botrytis cinerea ( B. cinerea ), Alternaria solani ( A. solani ), Rhizoctorzia solani ( R. solani ), Fusarium graminearum ( F. graminearum ), and Colletotrichum orbiculare ( C. orbiculare ). Specifically, the EC 50 values of 38 target compounds against R. solani were below 4 μg/mL, among which the compounds C13 (EC 50 = 0.49 μg/mL), C15 (EC 50 = 0.37 μg/mL), and C19 (EC 50 = 0.37 μg/mL) had the most prominent antifungal activity, superior to that of the control drug carbendazim (EC 50 = 0.52 μg/mL). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of the cellular ultrastructures of R. solani mycelia and cells after treatment with the compound C19 revealed sprawling growth of hyphae, a distorted outline of their cell walls, and reduced mitochondrial numbers. Studying the 3D-QSAR between the molecular structure and antifungal activity of 5-sulfonyl-1,3,4-thiadiazole-substituted flavonoid derivatives could significantly improve conventional drug molecular design pathways and facilitate the development of novel antifungal leads.

Dithiocarbamate fungicides have been widely used in agricultural practices due to their effective control of fungal diseases, thereby contributing to global food security and agricultural productivity. In this study, the inhibitory potency of eight compounds on human and rat aromatase (CYP19A1) activity was evaluated. The results revealed that zineb exhibited the highest inhibitory potency on human CYP19A1 (IC 50 , 2.79 μM). Maneb (IC 50 , 3.09 μM), thiram (IC 50 , 4.76 μM), and ferbam (IC 50 , 6.04 μM) also demonstrated potent inhibition on human CYP19A1. For the rat CYP19A1, disulfiram (IC 50 , 1.90 μM) displayed the strongest inhibition followed by maneb (2.16 μM), zineb (2.54 μM), and thiram (6.99 μM). These dithiocarbamates acted as mixed/non-competitive inhibitors of human and rat CYP19A1. Dithiothreitol (DTT), a reducing agent, partially rescued thiram-mediated inhibition when incubated at the same. Moreover, positive correlations were observed between log P , topological polar surface area, molecular weight, and heavy atoms and IC 50 values. 3D-QSAR analysis revealed the hydrogen bond acceptor and donor play critical roles in the binding of dithiocarbamates to human CYP19A1. In silico analysis showed that dithiocarbamates bind to the haem binding site, containing Cys437 residues. In conclusion, some dithiocarbamates potently inhibit human and rat CYP19A1 via interacting with haem-binding Cys437 residues.

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 R 2 of 0.95 and Q 2 LMO 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 Z 31 exhibited obvious in vitro antifungal activity with the EC 50 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 R 1 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 Z 31 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 Z 31 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cationic antimicrobial peptides (AMPs) possess broad-spectrum biological activities with less inclination to inducing antibiotic resistance. Herein a battery of amphiphilic amidines were designed by mimicking the characteristics of AMPs. The antifungal activities and the effects to the hyphal morphology and membrane permeability were investigated., Results: The results indicated the inhibitory rates of ten compounds were over 80% to Botrytis cinerea and ten compounds over 90% to Valsa mali Miyabe et Yamada at 50 mg L -1 . The half maximal effective concentration (EC 50 ) values of compound 5g and 6g to V. mali were 1.21 and 1.90 mg L -1 respectively. The protective rate against apple canker of compound 5g reached 93.4% at 100 mg L -1 on twigs, superior to carbendazim (53.3%). When treated with 5g, the cell membrane permeability and leakage of content of V. mali increased, accompanied with the decrease of superoxide dismutase (SOD) and catalase (CAT) level. Concurrently, the mycelial hyphae contracted, wrinkled, and collapsed, providing evidence of membrane perturbation. A three-dimensional quantitative structure-activity relationship (3D-QSAR) between the topic compounds and the EC 50 to V. mali was established showing good predictability (r 2  = 0.971)., Conclusion: Amphiphilic amidines can acquire antifungal activities by acting on the plasmic membrane. Compound 5g could be a promising lead in discovering novel fungicidal candidates. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Succinate dehydrogenase inhibitor (SDHI) fungicides play important roles in the control of plant fungal diseases. However, they are facing serious challenges from issues with resistance and cross-resistance, primarily attributed to their frequent application and structural similarities. There is an urgent need to design and develop SDHI fungicides with novel structures., Results: Aiming to discover novel potent SDHI fungicides, 31 innovative pyrazole β-ketonitrile derivatives with diphenyl ether moiety were rationally designed and synthesized, which were guided by a 3D-QSAR model from our previous study. The optimal target compound A23 exhibited not only outstanding in vitro inhibitory activities against Rhizoctonia solani with a half-maximal effective concentration (EC 50 ) value of 0.0398 μg mL -1 comparable to that for fluxapyroxad (EC 50  = 0.0375 μg mL -1 ), but also a moderate protective efficacy in vivo against rice sheath blight. Porcine succinate dehydrogenase (SDH) enzymatic inhibitory assay revealed that A23 is a potent inhibitor of SDH, with a half-maximal inhibitory concentration of 0.0425 μm. Docking study within R. solani SDH indicated that A23 effectively binds into the ubiquinone site mainly through hydrogen-bonds, and cation-π and π-π interactions., Conclusion: The identified β-ketonitrile compound A23 containing diphenyl ether moiety is a potent SDH inhibitor, which might be a good lead for novel fungicide research and optimization. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Plant fungal diseases pose a significant threat to crop production. The extensive use of chemical pesticides has led to growing environmental safety risks and pesticide resistance of various plant pathogens. Therefore, it is an urgent task to explore novel eco-friendly fungicidal agents with high efficacy to combat fungal infection., Results: In this study, we rationally designed a series of novel thymol derivatives by incorporation of the sulfonamide moiety and evaluated their biological activities against plant pathogenic fungi. The bioassay results underscored the remarkable in vitro antifungal activity of compounds 5m and 5t against Phytophthora capsici (P. capsici), with EC 50 values of 8.420 and 8.414 μg/mL, respectively. Their efficacies were superior to that of widely used commercial fungicides azoxystrobin (AZO, 20.649 μg/mL) and cabendazim (CAB, 251.625 μg/mL). Furthermore, compound 5v exhibited excellent in vitro antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum), with an EC 50 value of 12.829 μg/mL, significantly outperforming AZO (63.629 μg/mL). In vivo bioassays demonstrated the impactful activity of compound 5v against S. sclerotiorum, achieving over 98% curative and protective efficacies at the concentration of 200 μg/mL. Further mechanistic investigations unveiled that compound 5v induced mycelial shrinkage and collapse in S. sclerotiorum, resulting in organelle damage and the accumulation of antioxidant enzyme activity., Conclusion: The significant antifungal efficacy of the prepared thymol derivatives shall encourage further exploration of compound 5v as a promising candidate to develop novel fungicides for crop protection. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Tebuconazole (TEB), a prominent chiral triazole fungicide, has been extensively utilized for plant pathogen control globally. Despite experimental evidence of TEB metabolism in mammals, the enantioselectivity in the biotransformation of R- and S-TEB enantiomers by specific CYP450s remains elusive. In this work, integrated in silico simulations were employed to unveil the binding interactions and enantioselective metabolic fate of TEB enantiomers within human CYP1A2, 2B6, 2E1, and 3A4. Molecular dynamics (MD) simulations clearly delineated the binding specificity of R- and S-TEB to the four CYP450s, crucially determining their differences in metabolic activity and enantioselectivity. The primary driving force for robust ligand binding was identified as van der Waals interactions with CYP450s, particularly involving the hydrophobic residues. Mechanistic insights derived from quantum mechanics/molecular mechanics (QM/MM) calculations established C 2 -methyl hydroxylation as the predominant route of R-/S-TEB metabolism, while C 6 -hydroxylation and triazol epoxidation were deemed kinetically infeasible pathways. Specifically, the resulting hydroxy-R-TEB metabolite primarily originates from R-TEB biotransformation by 1A2, 2E1 and 3A4, whereas hydroxy-S-TEB is preferentially produced by 2B6. These findings significantly contribute to our comprehension of the binding specificity and enantioselective metabolic fate of chiral TEB by CYP450s, potentially informing further research on human health risk assessment associated with TEB exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Plant pathogens cause substantial crop losses annually, posing a grave threat to global food security. Fungicides have usually been used for their control, but the rapid development of pesticide resistance renders many ineffective, therefore the search for novel and efficient green pesticides to prevent and control plant diseases has become the top priority in crop planting., Results: The results of bioassay studies indicated that most of the target compounds showed certain antimicrobial activity in vitro. In particular, compound X7 showed high inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC 50 value of 27.47 μg mL -1 , surpassing conventional control agents such as thiazole zinc (41.55 μg mL -1 ) and thiodiazole copper (53.39 μg mL -1 ). Further studies on molecular docking showed that X7 had a strong binding affinity with 2FBW. The morphological change observed by scanning electron microscopy indicated that the surface of Xoo appears wrinkled and cracked under X7 treatment and a total of 2662 proteins were identified by label-free proteomic analysis. Three experiments have elucidated the mechanism whereby X7 induced considerable changes in the physiological and biochemical properties of Xoo, which in turn affected the reproduction and growth of bacteria., Conclusion: This work represents a pivotal advancement, offering important reference for the research and development therapeutics in combating plant pathogens. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Supervised field trial studies were conducted to understand dissipation kinetics and harvest time residues of a combination product of fluxapyroxad and pyraclostrobin in cumin plant/leaves and seeds at different locations in India. The results showed initial accumulation of fluxapyroxad at the levels of 15.4 and 20.2 mg kg -1 and pyraclostrobin at the level of 21.2 and 33.4 mg kg -1 in cumin leaves/plant in Anand, Gujarat. Fluxapyroxad and pyraclostrobin followed zero-order and first-order dissipation kinetics in cumin plant/leaves samples respectively. The residues translocated to cumin seeds. As the hazard quotient (HQ) was <1 in all cases consumer health risk may be negligible.

Background: To discover more efficient agricultural antimicrobial agents, a series of new quinazoline derivatives containing both a piperazine linker and the N-acetyl moiety were prepared and assessed for their antibacterial and antifungal activities., Results: All the target compounds were characterized by 1 H and 13 C NMR as well as high-resolution mass spectrometry (HRMS), and the chemical structure of the most potent compound E19 incorporating a 4-trifluoromethoxy substituent was clearly confirmed via single crystal X-ray diffraction measurements. The bioassay results indicated that some compounds possessed notable inhibitory effects in vitro against the bacterium Xanthomonas oryzae pv. oryzicola (Xoc). For example, compound E19 had an EC 50 (effective concentration for 50% activity) value of 7.1 μg/mL towards this pathogen, approximately 15- and 10-fold more effective than the commercial bactericides thiodiazole copper and bismerthiazol (EC 50  = 110.2 and 72.4 μg/mL, respectively). Subsequently, the mechanistic studies showed that compound E19 likely exerted its antibacterial efficacies by altering the cell morphology, increasing the permeability of bacterial cytoplasmic membrane, suppressing the production of bacterial extracellular polysaccharides and the extracellular enzyme activities (amylase and cellulase), and blocking the swimming motility of Xoc. Moreover, the proteomic analysis revealed that compound E19 could reduce the bacterial flagellar biosynthesis and decrease the flagellar motility by down-regulating the expression of the related differential proteins., Conclusion: Compound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Green mold is a common postharvest disease infected by Penicillium digitatum that causes citrus fruit decay, and severely affects fruit storage quality. This work aimed to investigate the antifungal activity of Sanxiapeptin against P. digitatum, and elucidate the possible mechanisms involved. Sanxiapeptin was capable of inhibiting spore germination, germ tube length and mycelial growth. The SYTOX green staining assay revealed that Sanxiapeptin targeted the fungal membrane, and changed the membrane permeability, leading to the leakage of cell constituents. Meanwhile, Sanxiapeptin could influence the cell wall permeability and integrity by increasing the activities of chitinase and glucanase, resulting in abnormal chitin consumption and the decrease of glucan. Intriguingly, Sanxiapeptin could effectively control postharvest decay in citrus fruits, and activate the host resistance responses by regulating the phenylpropanoid pathway. In conclusion, Sanxiapeptin exhibits multiphasic antifungal mechanisms of action to control green mold in citrus fruits, shows great potential as novel food preservatives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)