Azoxystrobin

Novel Flavonol Derivatives Containing 1,3,4-Thiadiazole as Potential Antifungal Agents: Design, Synthesis, and Biological Evaluation.[Pubmed:38645355]

ACS Omega. 2024 Apr 5;9(15):17297-17306.

In order to discover novel compounds with excellent agricultural activities, novel flavonol derivatives containing 1,3,4-thiadiazole were synthesized and evaluated for their antifungal activities. The bioassay results showed that some of the target compounds had good antifungal activities against Botrytis cinerea, Phomopsis sp. and Sclerotinia sclerotiorum in vitro. It is worth noting that the half-effective concentration (EC(50)) value of Y18 against B. cinerea was 2.4 mug/mL, which was obviously superior to that of Azoxystrobin (21.7 mug/mL). The curative activity of Y18 at 200 mug/mL (79.9%) was better than that of Azoxystrobin (59.1%), and its protective activity (90.9%) was better than that of Azoxystrobin (83.9%). Morphological studies by using scanning electron microscopy and fluorescence microscopy revealed that Y18 could affect the normal growth of B. cinerea mycelium. In addition, the mechanism of action studies indicated that Y18 could affect the integrity of cell membranes by inducing the production of endogenous reactive oxygen species and the release of the malondialdehyde content, leading to membrane lipid peroxidation and the release of cell contents. The inhibitory activity of flavonol derivatives containing 1,3,4-thiadiazole on plant fungi is notable, offering significant potential for the development of new antifungal agents.

Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in Botrytis cinerea.[Pubmed:38634420]

J Agric Food Chem. 2024 Apr 18.

Plant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the Azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with Azoxystrobin. The degradation half-life of Azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than Azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including Azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.

Combined effects of azoxystrobin and oxytetracycline on rhizosphere microbiota of Arabidopsis thaliana.[Pubmed:38626494]

Environ Int. 2024 Apr 14;186:108655.

The rhizosphere is one of the key determinants of plant health and productivity. Mixtures of pesticides are commonly used in intensified agriculture. However, the combined mechanisms underlying their impacts on soil microbiota remain unknown. The present study revealed that the rhizosphere microbiota was more sensitive to Azoxystrobin and oxytetracycline, two commonly used pesticides, than was the microbiota present in bulk soil. Moreover, the rhizosphere microbiota enhanced network complexity and stability and increased carbohydrate metabolism and xenobiotic biodegradation as well as the expression of metabolic genes involved in defence against pesticide stress. Co-exposure to Azoxystrobin and oxytetracycline had antagonistic effects on Arabidopsis thaliana growth and soil microbial variation by recruiting organic-degrading bacteria and regulating ABC transporters to reduce pesticide uptake. Our study explored the composition and function of soil microorganisms through amplicon sequencing and metagenomic approaches, providing comprehensive insights into the synergistic effect of plants and rhizosphere microbiota on pesticides and contributing to our understanding of the ecological risks associated with pesticide use.

Risk assessment and molecular mechanism of Sclerotium rolfsii resistance to boscalid.[Pubmed:38582572]

Pestic Biochem Physiol. 2024 Mar;200:105806.

Boscalid, a widely used SDHI fungicide, has been employed in plant disease control for over two decades. However, there is currently no available information regarding its antifungal activity against Sclerotium rolfsii and the potential risk of resistance development in this pathogen. In this study, we evaluated the sensitivity of 100 S. rolfsii strains collected from five different regions in China during 2018-2019 to boscalid using mycelial growth inhibition method and assessed the risk of resistance development. The EC(50) values for boscalid ranged from 0.2994 mug/mL to 1.0766 mug/mL against the tested strains, with an average EC(50) value of 0.7052 +/- 0.1473 mug/mL. Notably, a single peak sensitivity baseline was curved, indicating the absence of any detected resistant strains. Furtherly, 10 randomly selected strains of S. rolfsii were subjected to chemical taming to evaluate its resistance risk to boscalid, resulting in the successful generation of six stable and inheritable resistant mutants. These mutants exhibited significantly reduced mycelial growth, sclerotia production, and virulence compared to their respective parental strains. Cross-resistance tests revealed a correlation between boscalid and flutolanil, benzovindiflupyr, pydiflumetofen, fluindapyr, and thifluzamide; however, no cross-resistance was observed between boscalid and Azoxystrobin. Thus, we conclude that the development risk of resistance in S. rolfsii to boscalid is low. Boscalid can be used as an alternative fungicide for controlling peanut sclerotium blight when combined with other fungicides that have different mechanisms of action. Finally, the target genes SDHB, SDHC, and SDHD in S. rolfsii were initially identified, cloned and sequenced to elucidate the mechanism of S. rolfsii resistance to boscalid. Two mutation genotypes were found in the mutants: SDHD-D111H and SDHD-H121Y. The mutants carrying SDHD-H121Y exhibited moderate resistance, while the mutants with SDHD-D111H showed low resistance. These findings contribute to our comprehensive understanding of molecular mechanisms underlying plant pathogens resistance to SDHI fungicides.

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae.[Pubmed:38578751]

PLoS One. 2024 Apr 5;19(4):e0301519.

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

Toxic mechanisms of imazalil, azoxystrobin and their mixture to hook snout carp (Opsariichthys bidens).[Pubmed:38552970]

Sci Total Environ. 2024 May 20;926:172022.

While combinations of pesticides better represent actual conditions within aquatic ecosystems, the specific toxic effects of these combinations have not been determined yet. The objective of this research was to assess the combined impact of imazalil and Azoxystrobin on the hook snout carp (Opsariichthys bidens) and delve into the underlying causes. Our findings indicated that the 4-day LC(50) value for imazalil (1.85 mg L(-1)) was greater than that for Azoxystrobin (0.90 mg L(-1)). When imazalil and Azoxystrobin were combined, they presented a heightened effect on the species. Enzyme activities like SOD, CAT, GST, and CarE, along with androgen and estrogen levels, displayed marked differences in most single and combined treatments in comparison to the baseline group. Moreover, four genes (mn-sod, cu-sod, il-1, and esr) related to oxidative stress, immunity, and the endocrine system exhibited more pronounced expression changes when exposed to combined pesticides rather than individual ones. Our tests revealed that the combined use of imazalil and Azoxystrobin had more detrimental effect on aquatic vertebrates than when evaluated individually. This finding suggested that future ecological hazard analyses based only on individual tests might not sufficiently safeguard our aquatic ecosystems.

Development of a greenhouse assay to screen soybean varieties for resistance to aerial blight caused by Rhizoctonia solani AG1-IA.[Pubmed:38514043]

Phytopathology. 2024 Mar 21.

Aerial blight, caused by the fungus Rhizoctonia solani anastomosis group (AG) 1-IA, is an economically important soybean disease in the mid-Southern US. Management has relied on fungicide applications during the season, but there is an increasing prevalence of resistance to commonly used strobilurin fungicides and an urgent need to identify soybean varieties resistant to aerial blight. Since the patchy distribution of the pathogen complicates field variety screening, the present study aimed to develop a greenhouse screening protocol to identify soybean varieties resistant to aerial blight. For this, 88 pathogen isolates were collected from commercial fields and research farms across five Louisiana parishes, and 77% were confirmed to be R. solani AG1-IA. Three polymorphic co-dominant microsatellite markers were used to explore the genetic diversity of 43 R. solani AG1-IA isolates, which showed high genetic diversity with 35 haplotypes in total and only two haplotypes common to two other locations. Six genetically diverse isolates were chosen and characterized for their virulence and fungicide sensitivity. The isolate AC2 was identified as the most virulent and was resistant to both active ingredients, Azoxystrobin and pyraclostrobin, tested. The six isolates were used in greenhouse variety screening trials using a millet inoculation protocol. Of the 31 varieties screened, only Armor 48-D25 was classified as moderately resistant, and plant height to the first node influenced final disease severity. The study provides short-term solutions for growers to choose less susceptible varieties for planting and lays the foundation to characterize host resistance against this important soybean pathogen.

Effect of vine leaves processing on Azoxystrobin, Fenazaquin and Indoxacarb residues dissipation: processing factors and consumer safety assessment.[Pubmed:38513485]

Food Chem. 2024 Jul 30;447:139065.

The effect of vine leaves processing techniques on Azoxystrobin, Fenazaquin, and Indoxacarb residues was investigated. Residue extraction following field application of pesticides and leaf processing was carried out using the QuEChERS method, with analysis conducted by LC-MS/MS. In dry conservation, Azoxystrobin's half-life was estimated to exceed a year, Fenazaquin's was 18 days, and Indoxacarb's was 142 days. Azoxystrobin had a half-life of 261 days, Fenazaquin had a half-life of 9 days, and Indoxacarb's half-life exceeded a year in brine conservation. It is recommended to use dry conservation because it results in an average 60 % reduction in residue levels for the three pesticides. Boiling water significantly reduced pesticide residues (Azoxystrobin -40.3 %, Indoxacarb -22.4 %, and Fenazaquin -28.8 %). It is recommended to use boiling water for washing, as it shows an average removal rate of approximately 30 %. The health risk assessment indicated that consuming vine leaves posed no health risk for consumers, but overall exposure to residues must be considered.

Co-detection of azoxystrobin and thiabendazole fungicides in mold and mildew resistant wallboards and in children.[Pubmed:38509915]

Heliyon. 2024 Mar 13;10(6):e27980.

The study measured the levels of Azoxystrobin (AZ) and thiabendazole (TBZ) in wallboards and metabolite levels of these fungicides in children. The paper covering of wallboard samples contained a higher concentration of AZ and TBZ than the gypsum core, and similar amounts (w/w) of these two fungicides were present in the samples. These data suggest that commercial products containing a 1:1 (w/w) amount of AZ and TBZ, such as Sporgard(R) WB or Azo Tech, were applied to the wallboard paper. This is the first detection of TBZ in mold-and-mildew resistant wallboards. The TBZ metabolite, 5OH-TBZ, was detected in 48% of urine samples collected from children aged 40-84 months, and was co-detected with AZ-acid, a common AZ metabolite, in 37.5% of the urine samples. The detection frequency of 5OH-TBZ was positively associated with the detection frequency of AZ-acid. These findings suggest that certain types of wallboards used in homes and commercial buildings may be a potential source of co-exposure to AZ and TBZ in humans.

Design of a delivery vehicle chitosan-based self-assembling: controlled release, high hydrophobicity, and safe treatment of plant fungal diseases.[Pubmed:38504264]

J Nanobiotechnology. 2024 Mar 19;22(1):121.

BACKGROUND: Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. RESULTS: A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide Azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. CONCLUSIONS: This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides.

Single and combined exposure to 'bee safe' pesticides alter behaviour and offspring production in a ground-nesting solitary bee (Xenoglossa pruinosa).[Pubmed:38503336]

Proc Biol Sci. 2024 Mar 27;291(2019):20232939.

Mounting evidence supporting the negative impacts of exposure to neonicotinoids on bees has prompted the registration of novel 'bee-friendly' insecticides for agricultural use. Flupyradifurone (FPF) is a butenolide insecticide that shares the same mode of action as neonicotinoids and has been assessed to be 'practically non-toxic to adult honeybees' using current risk assessment procedures. However, these assessments overlook some routes of exposure specific to wild bees, such as contact with residues in soil for ground-nesters. Co-exposure with other pesticides may also lead to detrimental synergistic effects. In a fully crossed experiment, we assessed the possible lethal and sublethal effects of chronic exposure to two pesticides used on Cucurbita crops, the insecticide Sivanto Prime (FPF) and the fungicide Quadris Top (Azoxystrobin and difenoconazole), alone or combined, on solitary ground-nesting squash bees (Xenoglossa pruinosa). Squash bees exposed to Quadris Top collected less pollen per flower visit, while Sivanto-exposed bees produced larger offspring. Pesticide co-exposure induced hyperactivity in female squash bees relative to both the control and single pesticide exposure, and reduced the number of emerging offspring per nest compared to individual pesticide treatments. This study demonstrates that 'low-toxicity' pesticides can adversely affect squash bees under field-realistic exposure, alone or in combination.

Aggressive Alternaria brassicicola with reduced fungicide sensitivity can be associated with naturally infested broccoli seeds.[Pubmed:38499973]

Plant Dis. 2024 Mar 18.

Alternaria brassicicola is a part of Alternaria complex that causes leaf blight and head rot (ABHR) in brassica crops. Infested broccoli seeds can play an important role in introducing A. brassicicola in transplant houses and production fields. However, characterization of natural seed infestation and seed-to-seedling transmission of A. brassicicola in broccoli is yet to be demonstrated. In this research we characterized Alternaria spp. isolates from commercial broccoli seedlots for their species identity, pathogenicity and aggressiveness on broccoli and their sensitivity to Quinone-outside inhibitor (QoI) fungicide (Azoxystrobin). Two hundred commercial seedlots from two broccoli cultivars; Cultivar 1 (EC; n=100 seedlots) and Cultivar 2 (ED; n=100 seedlots) were evaluated for the presence of A. brassicicola under in-vitro conditions using a seedling grow-out assay. Alternaria spp. was detected in 31 and 28% of the commercial seedlots of Cultivar 1 and Cultivar 2, respectively. The seed-to-seedling transmission (%) varied considerably within each positive infested seedlot, which ranged from 1.3 to 17.3%. Subsequent molecular identification of single spore cultures (n=138) was made by sequencing four housekeeping genes; actin, the major allergen (Alta1), plasma membrane ATPase and Glyceraldehyde-3-phosphate dehydrogenase (GPD), and later the sequences were concatenated and compared for the phylogenetic distance with diverse Alternaria species. Ninety-six percent (n=133) of the isolates formed a cluster with a known A. brassicicola based on multigene phylogeny, which were later confirmed as A. brassicicola using a species-specific PCR assay. One hundred percent of the A. brassicicola seed isolates (n=133) were either highly- or moderately- aggressive on broccoli (cv. Emerald Crown) based on a detached leaf assay. Sensitivity of representative A. brassicicola isolates (n=58) to Azoxystrobin was evaluated using a spore germination assay and the EC50 values (effective fungicide concentration (ppm) at which germination of conidia of isolates were reduced by 50% compared to control) for each isolate was determined. A. brassicicola isolates from naturally infested commercial broccoli seeds were sensitive to Azoxystrobin with considerably low EC50 values in the range of <0.0001 ppm to 0.33 ppm; however, there were a few isolates (14%), which showed 100-fold reduced sensitivity from the most sensitive isolate (EC50 =0.0001 ppm). Our results confirm that commercial broccoli seedlots can be naturally contaminated with pathogenic and aggressive A. brassicicola. We also provide evidence for potential presence of A. brassicicola isolates with reduced Azoxystrobin-sensitivity in naturally infested commercial broccoli seedlots, which has never been reported before. Together, these findings may have implications in considerations for seed-health testing, seed treatments and greenhouse scouting to limit introduction of infested seedlots in commercial broccoli fields.

Organ-specific biotransformation in salmonids: Insight into intrinsic enzyme activity and biotransformation of three micropollutants.[Pubmed:38499104]

Sci Total Environ. 2024 May 15;925:171769.

Aquatic ecosystems continue to be threatened by chemical pollution. To what extent organisms are able to cope with chemical exposure depends on their ability to display mechanisms of defense across different organs. Among these mechanisms, biotransformation processes represent key physiological responses that facilitate detoxification and reduce the bioaccumulation potential of chemicals. Biotransformation does not only depend on the ability of different organs to display biotransformation enzymes but also on the affinity of chemicals towards these enzymes. In the present study, we explored the ability of different organs and of two freshwater fish to support biotransformation processes through the determination of in vitro phase I and II biotransformation enzyme activity, and their role in supporting intrinsic clearance and the formation of biotransformation products. Three environmentally relevant pollutants were evaluated: the polycyclic aromatic hydrocarbon (PAH) pyrene (as recommended by the OECD 319b test guideline), the fungicide Azoxystrobin, and the pharmaceutical propranolol. Comparative studies using S9 sub-cellular fractions derived from the liver, intestine, gills, and brain of brown trout (Salmo trutta) and rainbow trout (Oncorhynchus mykiss) revealed significant phase I and II enzyme activity in all organs. However, organ- and species-specific differences were found. In brown trout, significant extrahepatic biotransformation was observed for pyrene but not for Azoxystrobin and propranolol. In rainbow trout, the brain appeared to biotransform Azoxystrobin. In this same species, propranolol appeared to be biotransformed by the intestine and gills. Biotransformation products could be detected only from hepatic biotransformation, and their profiles and formation rates displayed species-specific patterns and occurred at different magnitudes. Altogether, our findings further contribute to the current understanding of organ-specific biotransformation capacity, beyond the expression and activity of enzymes, and its dependence on specific enzyme-chemical interactions to support mechanisms of defense against exposure.

Pesticides in surface water of the Ondas river watershed, western Bahia, Brazil: Spatial-seasonal distribution and risk assessment.[Pubmed:38490616]

Chemosphere. 2024 Apr;354:141659.

This study investigated the occurrence and seasonal distribution of different classes of pesticides in surface waters of the Ondas River Watershed, as well as potential risks to the aquatic health and human water consumption in the western region of Bahia state, Brazil. Two gas chromatography-mass spectrometry analytical methods were applied to monitor 34 pesticides in water samples collected during both the dry and rainy seasons at 17 sites. Upon individual analysis, only gamma-HCH, methoxychlor, demeton-S, methyl parathion, fenitrothion, chlorpyrifos, and Azoxystrobin exhibited statistically significant differences between seasons. During rainy season, concentration medians of residues were higher for gamma-HCH (74.7 ng L(-1)), methoxychlor (25.1 ng L(-1)), and Azoxystrobin (47.2 ng L(-1)), potentially linked to historical contamination or illegal use. Conversely, pesticides like methyl parathion, fenitrothion, and chlorpyrifos, belonging to the organophosphate class, showed higher concentration medians in the dry period, measuring 75.1, 5.50, and 10.8 ng L(-1), respectively, probably due to region crop activities. The risk quotient (RQ) assessment for aquatic life indicated that 59.0% of the samples in the dry season and 76.0% in the rainy season had RQ values greater than one, signifying a critical scenario for species conservation. Regarding human consumption, elevated risks were observed for heptachlor in both sampling periods and for Azoxystrobin during the rainy season, surpassing RQ levels above 1, indicating danger in untreated water ingestion. Additionally, 24.0% and 53.0% of the samples in the dry and rainy seasons, respectively, contained at least one pesticide exceeding the EU resolution limit (100 ng L(-1)). Therefore, considering this information, implementing mitigation measures to avoid the river's contamination becomes imperative.

Border cell population size and oxidative stress in the root apex of Triticum aestivum seedlings exposed to fungicides.[Pubmed:38478309]

Environ Sci Pollut Res Int. 2024 Apr;31(17):25600-25615.

Fungicides reduce the risk of mycopathologies and reduce the content of mycotoxins in commercial grain. The effect of fungicides on the structural and functional status of the root system of grain crops has not been studied enough. In this regard, we studied the phytocytotoxic effects tebuconazole (TEB) and epoxiconazole (EPO) and Azoxystrobin (AZO) in the roots of Triticum aestivum seedlings in hydroponic culture. In the presence of EPO and AZO (but not TEB) inhibition of the root growth was accompanied by a dose-dependent increase in the content of malondialdehyde, carbonylated proteins, and proline in roots. TEB was characterized by a dose-dependent decrease in the total amount of border cells (BCs) and the protein content in root extracellular trap (RET). For EPO and AZO, the dose curves of changes in the total number of BCs were bell-shaped. AZO did not affect the protein content in RET. The protein content in RET significantly decreased by 3 times for an EPO concentration of 1 microg/mL. The obtained results reveal that the BC-RET system is one of the functional targets of fungicides in the root system of wheat seedlings. Studied fungicides induce oxidative stress and structural and functional alterations in the BC-RET system that can affect their toxicity to the root system of crops.