ABSTRACT
In recent years, there has been a need for environmentally friendly compounds for weed management in agriculture. This study is aimed to assess the phytotoxic constituents of oils obtained from oleoresins of seven Copaifera species (known as copaiba oils). Copaiba oils were separated from the resins by hydro-distillation, and the distillates were analyzed using gas chromatography-mass spectrometry (GC-MS) to characterize their chemical compositions. Multivariate analyses and molecular networking of GC-MS data were conducted to discern patterns in the chemical composition and phytotoxic activity of the oils, with the aim of identifying key compounds associated with phytotoxic activity. Seed germination bioassay revealed strong or complete germination inhibition against the monocot, Agrostis stolonifera but not the dicot Lactuca sativa. GC-MS analysis showed variations in composition among Copaifera species with some common compounds identified across multiple species. Caryophyllene oxide and junenol were associated with the observed phytotoxic effects. Automated flash chromatography was used to isolate the major compounds of the oils. Isolated compounds exhibited differing levels of phytotoxicity compared to the oils, suggesting the importance of interactions or synergism among oil components. These findings highlight the potential of copaiba oils as natural herbicidal agents and underscore the importance of considering species-specific responses in weed management strategies.
Subject(s)
Fabaceae , Gas Chromatography-Mass Spectrometry , Germination , Oils, Volatile , Seeds , Fabaceae/chemistry , Oils, Volatile/chemistry , Oils, Volatile/toxicity , Oils, Volatile/pharmacology , Seeds/chemistry , Seeds/drug effects , Seeds/growth & development , Germination/drug effects , Plant Oils/chemistry , Plant Oils/toxicity , Plant Oils/pharmacology , Lactuca/drug effects , Lactuca/growth & development , Herbicides/pharmacology , Herbicides/chemistry , Herbicides/toxicityABSTRACT
A bacterium growing on infected leaves of Hydrocotyle umbellata, commonly known as dollarweed, was isolated and identified as Pantoea ananatis. An ethyl acetate extract of tryptic soy broth (TSB) liquid culture filtrate of the bacterium was subjected to silica gel chromatography to isolate bioactive molecules. Indole was isolated as the major compound that gave a distinct, foul odor to the extract, together with phenethyl alcohol, phenol, tryptophol, N-acyl-homoserine lactone, 3-(methylthio)-1-propanol, cyclo(L-pro-L-tyr), and cyclo(dehydroAla-L-Leu). This is the first report of the isolation of cyclo(dehydroAla-L-Leu) from a Pantoea species. Even though tryptophol is an intermediate in the indoleacetic acid (IAA) pathway, we were unable to detect or isolate IAA. We investigated the effect of P. ananatis inoculum on the growth of plants. Treatment of Lemna paucicostata Hegelm plants with 4 × 109 colony forming units of P. ananatis stimulated their growth by ca. five-fold after 13 days. After 13 days of treatment, some control plants were browning, but treated plants were greener and no plants were browning. The growth of both Cucumis sativus (cucumber) and Sorghum bicolor (sorghum) plants was increased by ca. 20 to 40%, depending on the growth parameter and species, when the rhizosphere was treated with the bacterium after germination at the same concentration. Plant growth promotion by Pantoea ananatis could be due to the provision of the IAA precursor indole.
Subject(s)
Alcohols , Centella , Indoles , Pantoea , Pantoea/chemistry , Pantoea/metabolism , Plants/microbiologyABSTRACT
Low glyphosate doses that produce hormesis may alter the susceptibility to herbicides of weeds or enhance their propagation and dispersal. The objective of this work was to evaluate the hormetic effects of glyphosate on the vegetative, phenological and reproductive development in resistant (R) and susceptible (S) Conyza sumatrensis biotypes. The glyphosate resistance level of biotype R was 11.2-fold compared to the S biotype. Glyphosate doses <11.25 g ae ha-1 induced temporary and permanent hormetic effects for the number of leaves, plant height and dry mass accumulation up to 28 d after application in both R and S biotypes. The S biotype required 15-19% fewer thermal units at 1.4 and 2.8 g ae ha-1 glyphosate than untreated plants to reach the bolting stage. Also, this biotype had less thermal units associated with the appearance (1225 vs 1408 units) and opening (1520 vs 1765 units) of the first capitulum than the R biotype. In addition, glyphosate affected reproductive traits of both biotypes compared to their controls, increasing the number of capitulum's and seeds per plant up to 37 and 41% (at 2.8 and 0.7 g ae h-1, respectively) in the S biotype, and by 48 and 114% (both at 5.6 g ae ha-1) in the R biotype. Depending on environmental parameters, glyphosate may or may not cause hormetic effects on the vegetative and phenological development of C. sumatrenis biotypes; however, this herbicide increases the speed and fecundity of reproduction, regardless of the glyphosate susceptibility level, which can alter the population dynamics and glyphosate susceptibility of future generations.
Subject(s)
Conyza , Herbicides , Glyphosate , Glycine/toxicity , Hormesis , Herbicide Resistance , Herbicides/toxicity , PlantsABSTRACT
As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, a series of new pyrazole acyl(thio)urea compounds containing a diphenyl motif were designed and synthesized. Their structures were confirmed by 1H NMR, HRMS, and single X-ray crystal diffraction analysis. Most of these compounds possessed excellent activity against 10 fungal plant pathogens at 50 µg mL-1, especially against Rhizoctonia solani, Alternaria solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Cercospora arachidicola. Interestingly, compounds 3-(difluoromethyl)-1-methyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9b, EC50 = 0.97 ± 0.18 µg mL-1), 1,3-dimethyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9a, EC50 = 2.63 ± 0.41 µg mL-1), and N-((4'-chloro-[1,1'-biphenyl]-2-yl)carbamoyl)-1,3-dimethyl-1H-pyrazole-4-carboxamide (9g, EC50 = 1.31 ± 0.15 µg mL-1) exhibited activities against S. sclerotiorum that were better than the commercial fungicide bixafen (EC50 = 9.15 ± 0.05 µg mL-1) and similar to the positive control fluxapyroxad (EC50 = 0.71 ± 0.11 µg mL-1). These compounds were not significantly phytotoxic to monocotyledonous and dicotyledonous plants. Structure-activity relationships (SAR) are discussed by substituent effects/molecular docking, and density functional theory analysis indicated that these compounds are succinate dehydrogenase inhibitors.
Subject(s)
Biphenyl Compounds , Fungicides, Industrial , Succinate Dehydrogenase , Urea , Molecular Docking Simulation , Structure-Activity Relationship , Fungicides, Industrial/chemistry , Pyrazoles/chemistry , Antifungal Agents/pharmacologyABSTRACT
The Catalogue Of Somatic Mutations In Cancer (COSMIC), https://cancer.sanger.ac.uk/cosmic, is an expert-curated knowledgebase providing data on somatic variants in cancer, supported by a comprehensive suite of tools for interpreting genomic data, discerning the impact of somatic alterations on disease, and facilitating translational research. The catalogue is accessed and used by thousands of cancer researchers and clinicians daily, allowing them to quickly access information from an immense pool of data curated from over 29 thousand scientific publications and large studies. Within the last 4 years, COSMIC has substantially expanded its utility by adding new resources: the Mutational Signatures catalogue, the Cancer Mutation Census, and Actionability. To improve data accessibility and interoperability, somatic variants have received stable genomic identifiers that are associated with their genomic coordinates in GRCh37 and GRCh38, and new export files with reduced data redundancy have been made available for download.
Subject(s)
Databases, Genetic , Genomics , Neoplasms , Humans , Databases, Factual , Knowledge Bases , Mutation , Neoplasms/genetics , Databases, Genetic/trends , InternetABSTRACT
Microbial biopesticides to control plant pathogens and insects in crops have had significant success. However, there have been relatively few successes for microbial bioherbicides in crops, despite considerable numbers of publications and commercial product introductions in this area. Marketed microbial bioherbicide products for use in agriculture have been largely unsuccessful. This article covers the potential advantages of successful microbial bioherbicides, as well as the biological and technical issues that have limited their success. Technologies to overcome the problems that have limited the success of these products are discussed. The many advantages of using killed microbial products (e.g. cell-free filtrates) over living microbial products as bioherbicides are detailed. A commercialized mycoherbicide that has been selected for in the laboratory for control of the parasitic weed Striga hermonthica is being used with some success in Africa, indicating that non-transgenic modification of the genetics of bioherbicide microbes for improved efficacy is acceptable to some regulatory authorities. Genetic modifications to improve efficacy and host range, as well as improved application technology to greatly reduce the amount of product needed are two technologies that are likely to expand the use of microbial bioherbicides in the future. © 2023 Society of Chemical Industry.
Subject(s)
Plant Weeds , Striga , Plant Weeds/genetics , Crops, Agricultural/genetics , Agriculture , Biological Control Agents , Weed ControlABSTRACT
The identification of natural and environmentally friendly pesticides is a key area of interest for the agrochemical industry, with many potentially active compounds being sourced from numerous plant species. In this study, we report the bioassay-guided isolation and identification of phytotoxic and antifungal compounds from the ethyl acetate extract of Helietta parvifolia stems. We identified eight compounds, consisting of two coumarins and six alkaloids. Among these, a new alkaloid, 2-hydroxy-3,6,7-trimethoxyquinoline-4-carbaldehyde (6), was elucidated, along with seven known compounds. The phytotoxicity of purified compounds was evaluated, and chalepin (4) was active against Agrostis stolonifera at 1 mM with 50% inhibition of seed germination and it reduced Lemna pausicotata (duckweed) growth by 50% (IC50) at 168 µM. Additionally, we evaluated the antifungal activity against the fungal plant pathogen Colletotrichum fragariae using a thin-layer chromatography bioautography assay, which revealed that three isolated furoquinoline alkaloids (flindersiamine (3), kokusagenine (7), and maculine (8)) among the isolated compounds had the strongest inhibitory effects on the growth of C. fragariae at all tested concentrations. Our results indicate that these active natural compounds, i.e., (3), (4), (7), and (8), could be scaffolds for the production of more active pesticides with better physicochemical properties.
Subject(s)
Alkaloids , Pesticides , Antifungal Agents/pharmacology , Plant Extracts/chemistry , Alkaloids/pharmacology , PlantsABSTRACT
MOTIVATION: Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. To evaluate the mutational signatures operative in a cancer genome, one first needs to quantify their activities by estimating the number of mutations imprinted by each signature. RESULTS: Here we present SigProfilerAssignment, a desktop and an online computational framework for assigning all types of mutational signatures to individual samples. SigProfilerAssignment is the first tool that allows both analysis of copy-number signatures and probabilistic assignment of signatures to individual somatic mutations. As its computational engine, the tool uses a custom implementation of the forward stagewise algorithm for sparse regression and nonnegative least squares for numerical optimization. Analysis of 2700 synthetic cancer genomes with and without noise demonstrates that SigProfilerAssignment outperforms four commonly used approaches for assigning mutational signatures. AVAILABILITY AND IMPLEMENTATION: SigProfilerAssignment is available under the BSD 2-clause license at https://github.com/AlexandrovLab/SigProfilerAssignment with a web implementation at https://cancer.sanger.ac.uk/signatures/assignment/.
Subject(s)
Neoplasms , Humans , Mutation , Neoplasms/genetics , Algorithms , GenomeABSTRACT
New fungicide modes of action are needed for fungicide resistance management strategies. Several commercial herbicide targets found in fungi that are not utilized by commercial fungicides are discussed as possible fungicide molecular targets. These are acetyl CoA carboxylase, acetolactate synthase, 5-enolpyruvylshikimate-3-phosphate synthase, glutamine synthase, phytoene desaturase, protoporphyrinogen oxidase, long-chain fatty acid synthase, dihydropteroate synthase, hydroxyphenyl pyruvate dioxygenase, and Ser/Thr protein phosphatase. Some of the inhibitors of these herbicide targets appear to be either good fungicides or good leads for new fungicides. For example, some acetolactate synthase and dihydropteroate inhibitors are excellent fungicides. There is evidence that some herbicides have indirect benefits to certain crops due to their effects on fungal crop pathogens. Using a pesticide with both herbicide and fungicide activities based on the same molecular target could reduce the total amount of pesticide used. The limitations of such a product are discussed.
Subject(s)
Acetolactate Synthase , Fungicides, Industrial , Herbicides , Herbicides/pharmacology , Fungicides, Industrial/pharmacology , Herbicide Resistance , Protoporphyrinogen Oxidase , 3-Phosphoshikimate 1-Carboxyvinyltransferase , Acetolactate Synthase/metabolismABSTRACT
Natural products are a main source of new chemical entities for use in drug and pesticide discovery. In order to discover lead compounds with high herbicidal activity, a series of new pyrido[2,3-d] pyrimidine derivatives were designed and synthesized using 2-chloronicotinic acid as the starting material. Their structures were characterized with 1H NMR, 13C NMR and HRMS, and the herbicidal activities against dicotyledonous lettuce (Lactuca sativa), field mustard (Brassica campestris), monocotyledonous bentgrass (Agrostis stolonifera) and wheat (Triticum aestivum) were determined. The results indicated that most of the pyrido[2,3-d] pyrimidine derivatives had no marked inhibitory effect on lettuce at 1 mM. However, most of the pyrido[2,3-d] pyrimidine derivatives possessed good activity against bentgrass at 1 mM. Among them, the most active compound, 3-methyl-1-(2,3,4-trifluorophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2o), was as active as the positive controls, the commercial herbicides clomazone and flumioxazin. Molecular simulation was performed with molecular docking and DFT calculations. The docking studies provided strong evidence that 2o acts as an herbicide by inhibition of protoporphyrinogen oxidase. However, the physiological results indicate that it does not act on this target in vivo, implying that it could be metabolically converted to a compound with a different molecular target.
Subject(s)
Brassica , Herbicides , Herbicides/chemistry , Molecular Docking Simulation , Pyrimidines/pharmacology , Pyrimidines/chemistry , Brassica/metabolism , Protoporphyrinogen Oxidase , Structure-Activity RelationshipABSTRACT
Khellin and visnagin furanochromones were recently reported as potential new bioherbicides with phytotoxic activities comparable to those of some commercially available herbicides. In this study, we examined the effect of O-alkylation and O-arylalkylation of both khellin and visnagin on its effect on herbicidal and antifungal activity. Synthetic analogues included O-demethyl khellin and visnagin, acetylated O-demethyl khellin and visnagin, O-benzylated demethyl khellin and visnagin, four O-demethyl alkylated khellin analogues, and six O-demethyl alkylated visnagin analogues, many of which are reported here for the first time. Both acetate analogues of khellin and visnagin indicated more activity as herbicides on Lemna pausicostata than visnagin, with IC50 values of 71.7 and 77.6 µM, respectively. Complete loss of activity for all O-alkyl analogues with a carbon chain length of greater than 14 carbons was observed. The O-demethyl butylated visnagin analogue was the most active compound with an IC50 of 47.2 µM against L. pausicostata. O-Demethyl ethylated analogues of both khellin and visnagin were as effective as khellin. In the antifungal bioautography bioassay against Colletotrichum fragariae at 100 µg, the only active O-alkyl and O-arylalkyl analogues were O-ethylated, O-butylated, and O-benzylated visnagin analogues with zones of inhibition of 10, 9, and 9 mm, respectively, an effect comparable to that of visnagin and khellin.
ABSTRACT
Inhibitors targeting the 4-hydroxyphenyl pyruvate dioxygenase (HPPD) enzyme are well established herbicides and HPPD is also a primary enzyme within the tyrosine metabolism pathway in hematophagous arthropods, which is an essential metaboilic pathway post-blood feeding to prevent tyrosine-mediated toxicity. The objective of this study was to characterize the toxicity of triketone, pyrazole, pyrazolone, isoxazole, and triazole herbicides that inhibit HPPD to blood-fed mosquitoes and ticks. Topical exposure of nitisinone to blood-fed Aedes aegypti yielded high toxicity with an LD50 of 3.81 ng/insect (95% CI: 3.09 to 4.67 ng; Hillslope: 0.97, r2: 0.99), yet was non-toxic to non-blood fed (NBF) mosquitoes. The rank order of toxicity was nitisinone > tembotrione > pyrazoxyfen > tebuconazole > mesotrione against blood-fed Ae. Aegypti, but nitisinone was approximately 30-fold more toxic than other chemicals tested. We also assessed the toxicity of HPPD-inhibiting herbicides to the lone star tick, Amblyomma americanum and similarly, nitisinone was toxic to Am. americanum with a lethal time to kill 50% of subjects (LT50) of 23 h at 10 µM. Knockdown of the gene encoding the HPPD enzyme was performed through RNA-interference led to significant mortality after blood feeding in both, Ae. aegypti and Am. americanum. Lastly, a fluorescence assay was developed to determine relative quantities of L-tyrosine in Ae. aegypti and Am. americanum treated with HPPD inhibitors. L-tyrosine levels correlated with toxicity with nitisinone exposure leading to increased tyrosine concentrations post-blood feeding. Taken together, these data support previous work suggesting HPPD-inhibitors represent a novel mode of toxicity to mosquitoes and ticks and may represent base scaffolds for development of novel insecticides specific for hematophagous arthropods.
Subject(s)
4-Hydroxyphenylpyruvate Dioxygenase , Aedes , Herbicides , Animals , Herbicides/pharmacology , Amblyomma , Aedes/metabolism , Tyrosine/metabolism , Enzyme InhibitorsABSTRACT
New insecticide modes of action are needed for insecticide resistance management strategies. The number of molecular targets of commercial herbicides and insecticides are fewer than 35 for both. Few commercial insecticide targets are found in plants, but ten targets of commercial herbicides are found in insects. For several of these commonly held targets, some compounds kill both plants and insects. For example, herbicidal inhibitors of p-hydroxyphenylpyruvate dioxygenase are effective insecticides on blood-fed insects. The glutamine synthetase-inhibiting herbicide glufosinate is insecticidal by the same mechanism of action, inhibition of glutamine synthetase. These and other examples of shared activities of commercial herbicides with insecticides through the same target site are discussed. Compounds with novel herbicide targets shared by insects that are not commercialized as pesticides (such as statins) are also discussed. Compounds that are both herbicidal and insecticidal can be used for insect pests not associated with crops or with crops made resistant to the compounds.
Subject(s)
Herbicides , Insecticides , Pesticides , Animals , Herbicides/pharmacology , Insecticides/pharmacology , Glutamate-Ammonia Ligase , InsectaABSTRACT
The continuing need to protect food and fiber production to address the demands of an expanding global population requires new pest management tools for crop protection. Natural products (NPs) have been and continue to be a key source of inspiration for new active ingredients (AIs) for crop protection, accounting for 17% of all crop protection AIs. However, potentially 50% of all crop protection compounds have or could have a NP origin if NP synthetic equivalents (NPSEs, synthetic compounds discovered by other approaches but for which a NP model also happens to exist) are also considered. The real and hypothetical NPs have their greatest impact as insight for new classes of crop protection compounds. Among the different product areas, NPs have their largest influence on the discovery of new insecticides, while herbicides have been the least affected by mining NPs for new AIs. While plants have historically been the largest (60% of the total) source of NPs of AIs for crop protection, in the last 30 years, bacterial NPs have become the largest source (42% of the total) of new classes (first in class) of NP-inspired crop protection AIs. Interest in NPs for crop protection continues, an aspect that is highlighted by the notable rise in the numbers of publications and patents on this topic, especially in the last 20 years. The present analysis further illustrates the continuing interest and value in NPs as sources of and inspiration for new classes of crop protection compounds.
Subject(s)
Biological Products , Herbicides , Insecticides , Crop Protection , Pest ControlABSTRACT
A new series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. CPD is an inhibitor of ketol-acid reductoisomerase (KARI), an enzyme of the branched chain amino acid pathway in plants. The structures of CPD analogues were characterized by 1H NMR and HRMS. The structure of N,N'-bis(4-(tert-butyl)phenyl)cyclopropane-1,1-dicarboxamide was further elucidated by X-ray diffraction. The herbicidal activities of these compounds were tested against lettuce (Lactuca sativa) and bentgrass (Agrostis stolonifera). Most of these compounds exhibited low herbicidal activity against both plant species. Among them, N,N'-bis(2-ethylphenyl)cyclopropane-1,1-dicarboxamide displayed moderate activity against bentgrass. Inhibition of KARI activity by the CPD analogues was also assessed experimentally and by molecular docking simulation with results supporting inhibition of KARI as their mode of action. These results provide the basis for design of more effective KARI inhibitors.