Herbicide Discovery Research Articles

Allelopathic prospective of Ricinus communis and Jatropha curcas for bio-control of weeds

Ricinus communis and Jatropha curcas (Euphorbiaceae), two biodiesel plants are especially well known for many industrial, pharmacological, and/or toxicological properties, but to date very little is known about their allelopathic characteristics. Hence, to explore the allelopathy of both plants, the aqueous methanol extracts of their leaves were examined at five different concentrations (3-, 10-, 30-, 100-, and 300-mg dry weight [DW] equivalent extract/mL) on the seedling growth of cress, lettuce, alfalfa, Italian ryegrass, barnyard grass, and crabgrass, and on the germination of cress and barnyard grass. The bioassay experiments were conducted in a completely randomized design with three replications. The inhibitory activities of both extracts depends on the concentration and test plant species. Considering the I50 values, the seedling growth of lettuce was most sensitive to both extracts and barnyard grass was least sensitive. At concentration of 300-mg DW equivalent extract/mL, R. communis completely inhibited the germination of both cress and barnyard grass, and the seedling growth of cress, lettuce, Italian ryegrass, and barnyard grass. At the same concentration, complete inhibition on the germination of cress and the seedling growth of lettuce and alfalfa was only observed by J. curcas extracts. These results suggest that both plants have allelopathic properties and may possess allelochemicals. Since R. communis extracts had greater activity than J. curcas against the major crop weeds, this plant could be the best candidate for isolation and identification of allelochemicals, which might promote the discovery of new natural herbicides for sustainable agriculture.

The Structure-Based Three-Dimensional Pharmacophore Models for Arabidopsis thaliana HPPD inhibitors as Herbicide

Division of Convergence Chemistry, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, KoreaReceived June 24, 2013, Accepted July 5, 2013p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a potent herbicide target that is in current use. In this study,we developed a predictive pharmacophore model that uses known HPPD inhibitors based on a theoreticallyconstructed HPPD homology model. The pharmacophore model derived from the three-dimensional (3D)structure of a target protein provides helpful information for analyzing protein-ligand interactions, leading tofurther improvement of the ligand binding affinity.Key Words : HPPD, Herbicide, Pharmacophore, Molecular dockingIntroductionThe success rate for herbicidal discovery in agriculturalresearch has been decreasing in recent years. Thus, there isan urgent need for innovation in the area of herbicide dis-covery. Accordingly, a paramount goal for modern herbicideresearch is to discover a new potent target that severelydisrupts a plant’s metabolism by inhibiting essential enzymesfor growth. The successful design of a novel herbicidedepends on selectivity and safety issues. Selective herbicidetargets are usually single enzymes in plants with a conven-tional mode of action. By uniquely binding to the active siteof the target protein, the inhibition activity should affectunwanted weeds and thus protect agricultural products.Regarding the safety issue, the herbicide should follow stricttoxicity regulations to mitigate any harmful effects on humans.

Synthesis of novel heterocyclic acetyl coenzyme-A carboxylase inhibitors via a Claisen rearrangement

Abstract The synthesis of functionalized heteroaromatic compounds is of high importance in the discovery of novel herbicides. In this Letter is reported the synthesis of a series of 2-heteroaromatic-1,3-diones utilizing a Claisen rearrangement to form a key carbon–carbon bond. The paper focuses on the scope and diversity of the molecules synthesized via this route.

Phytotoxicity of leaf aqueous extract of Rapanea umbellata (Mart.) Mez (Primulaceae) on weeds

Allelopathic substances can be used to develop weed control alternatives based on natural products. The objective of this study was to compare the phytotoxic activity of aqueous leaf extracts of Rapanea umbellata with the toxicity of a synthetic herbicide on the germination and growth of weed species. The weeds species barnyard grass (Echinochloa crus-galli), wild poinsettia (Euphorbia heterophylla) and morning glory (Ipomoea grandifolia) were used. The effects of the aqueous leaf extract of R. umbellata at concentrations of 10% and 5% (g mL -1 ) were compared to the control (distilled water) and to the synthetic herbicide oxyfluorfen. The average weed germination time was significantly lower (p < 0.05) in control than in extract and herbicide treatments. The herbicide had more significant effects than the extract on the initial growth of the aerial part. However, the initial growth of the root part was significantly more affected by the leaf extract than by the herbicide. The extract also caused many disorders in weed root anatomy. Therefore, the leaf aqueous extract of R. umbellata showed important results that indicate that it should be bioprospected and that its allelochemicals should be purified for the discovery of natural-origin herbicides.

Identification and Characterization of Herbicide from Pileostegia viburnoides var.glabrescens

Increasing resistance to agrochemicals by insects and plant pathogens and the loss of weed and disease control agents are factors that drive the need to search for new natural product derived plant protestants and agrochemicals. Bio-prospecting natural products allows discovery of new agrochemicals for pest management and chemistry found from plants used worldwide in traditional medicines have not been evaluated as potential bio-pesticides or new plant growth regulators. Pileostegia viburnoides var. glabrescens is a traditional Chinese medicine plant used for treating traumatic injury and fractures. Preliminary evaluations of P. viburnoides var. glabrescens was completed in 2012 for antifungal and herbicidal activity. N-Butanol extract from P. viburnoides var. glabrescens was shown to be active at higher concentrations to Agrostis (monocot) and less active against lettuce (dicots). Several pure compounds were separated by chromatography from n-butanol extract of P. viburnoides var. glabrescens. The pure compound skimmin in the active fractions obtained from n-butanol extract was identified. These fractions and skimmin showed phytotoxic activity against Iceberg lettuce and Agrostis seeds in primary research. Skimmin possessed high seed germination inhibition of monocot species and moderate seed germination inhibition against the dicot species. Therefore, we began a more in-depth evaluation of 8 pure compounds obtained from the active n-butanol extract of P. viburnoides and skimmin. Following natural product leads offers an efficient approach to discovering and optimizing new herbicides for weed management. Due to the continuing development of chemical resistance in agriculture, discovery of new herbicides is an important research objective. Natural product based herbicides with low mammalian and environmental toxicity will help guarantee food safety and sustainability of U.S. and Chinese agriculture.

Crystallization and preliminary X-ray characterization of the tetrapyrrole-biosynthetic enzyme porphobilinogen deaminase from Arabidopsis thaliana.

The enzyme porphobilinogen deaminase (PBGD; hydroxymethylbilane synthase; EC 2.5.1.61) catalyses a key early step of the haem-biosynthesis pathway in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole. The enzyme possesses a dipyrromethane cofactor which is covalently linked by a thioether bridge to an invariant cysteine residue. Since PBGD catalyses a reaction which is common to the biosynthesis of both haem and chlorophyll, structural studies of a plant PBGD enzyme offer great potential for the discovery of novel herbicides. Until recently, structural data have only been available for the Escherichia coli and human forms of the enzyme. Expression in E. coli of a codon-optimized gene for Arabidopsis thaliana PBGD has permitted for the first time the crystallization and preliminary X-ray analysis of the enzyme from a plant species at high resolution.

Transfer of Auxinic Herbicide Resistance from Wild Mustard (Sinapis arvensis) into Radish (Raphanus sativus) through Embryo Rescue

The discovery of auxinic herbicides (e.g., 2,4-D, Dicamba, Picloram) for selective control of broad-leaf weeds in cereal crops revolutionized modern agriculture. These herbicides are inexpensive and do not generally have prolonged residual activity in soil. Although cultivated species of Brassicaceae (e.g., radish and other vegetables) are susceptible to auxinic herbicides, some biotypes of wild mustard (Sinapis arvensis, 2n = 18) were found to be highly resistant to Picloram and Dicamba. Inter-generic hybrids between wild mustard and radish (Raphanus sativus, 2n = 18) were produced by traditional breeding coupled with in vitro embryo rescue/ovule culture. To increase frequency of embryo regeneration and hybrid plant production, several hundred reciprocal crosses were performed between these species. Upon altering cultural conditions and media composition, a high frequency of embryo regeneration and hybrid plant establishment was achieved. A protocol was also optimized for in vitro clonal multiplication of inter-generic hybrids produced by embryo rescue. To evaluate transfer of auxinic herbicide resistance from wild mustard into hybrid plants, several screening tests (involving in vitro, molecular-based as well as whole plant-based tests) were performed. Results indicated that hybrids of R. sativus x S. arevensis were resistant to auxinic herbicides suggesting, that, the resistance trait was transferred to these hybrids from the wild mustard. This research for the first time demonstrates the possibility of transfer of auxinic herbicide resistance from wild mustard to radish.

Innovation: Changing Trends in Herbicide Discovery

Innovation: Changing Trends in Herbicide Discovery

A perspective on the role of quantitative structure–activity and structure–property relationships in herbicide discovery

For the last 15 years the agrochemical industry has focused on using genetic modification to put genes that confer resistance to existing commercial herbicides into crop plants rather than on discovering new herbicides with novel modes of action. The widespread appearance of weeds resistant to those herbicides is now causing the industry to revive their herbicide discovery programs. Elucidation of quantitative structure-activity relationships (QSARs) played a major role in the discovery and development of existing commercial herbicides, but the advent of genetically modified crops has caused published work (at least) in the area to drift from the industrial arena into academic studies. The focus has also turned inward, to refining models for established herbicide targets instead of elucidating new ones. This perspective highlights the importance of QSARs and quantitative structure-property relationships (QSPRs) to herbicide discovery in an historical context and provides some guidance as to how they might profitably be applied going forward.

Why have no new herbicide modes of action appeared in recent years?

Herbicides with new modes of action are badly needed to manage the evolution of resistance of weeds to existing herbicides. Yet no major new mode of action has been introduced to the market place for about 20 years. There are probably several reasons for this. New potential products may have remained dormant owing to concerns that glyphosate-resistant (GR) crops have reduced the market for a new herbicide. The capture of a large fraction of the herbicide market by glyphosate with GR crops led to significantly diminished herbicide discovery efforts. Some of the reduced herbicide discovery research was also due to company consolidations and the availability of more generic herbicides. Another problem might be that the best herbicide molecular target sites may have already been discovered. However, target sites that are not utilized, for which there are inhibitors that are highly effective at killing plants, suggests that this is not true. Results of modern methods of target site discovery (e.g. gene knockout methods) are mostly not public, but there is no evidence of good herbicides with new target sites coming from these approaches. In summary, there are several reasons for a long dry period for new herbicide target sites; however, the relative magnitude of each is unclear. The economic stimulus to the herbicide industry caused by the evolution of herbicide-resistant weeds, especially GR weeds, may result in one or more new modes of action becoming available in the not too distant future.

Herbicide Resistances in Amaranthus tuberculatus: A Call for New Options

Amaranthus tuberculatus is a major weed of crop fields in the midwestern United States. Making this weed particularly problematic to manage is its demonstrated ability to evolve resistance to herbicides. Herbicides to which A. tuberculatus has evolved resistance are photosystem II inhibitors, acetolactate synthase inhibitors, protoporphyrinogen oxidase inhibitors, and glyphosate. Many populations of A. tuberculatus contain more than one of these resistances, severely limiting the options for effective herbicide control. A survey of multiple-herbicide resistance in A. tuberculatus revealed that all populations resistant to glyphosate contained resistance to acetolactate synthase inhibitors, and 40% contained resistance to protoporphyrinogen oxidase inhibitors. The occurrences of multiple-herbicide resistances in A. tuberculatus illustrate the need for continued herbicide discovery efforts and/or the development of new strategies for weed management.

Phytotoxicity of Sarmentine Isolated from Long Pepper (Piper longum) Fruit

Discovery of novel natural herbicides has become crucial to overcome increasing weed resistance and environmental issues. In this article, we describe the finding that a methanol extract of dry long pepper (Piper longum L.) fruits is phytotoxic to lettuce (Lactuca sativa L.) seedlings. The bioassay-guided fractionation and purification of the crude extract led to isolation of sarmentine (1), a known compound, as the active principle. Phytotoxicity of 1 was examined with a variety of seedlings of field crops and weeds. Results indicated that 1 was a contact herbicide and possessed broad-spectrum herbicidal activity. Moreover, a series of sarmentine analogues were then synthesized to study the structure-activity relationship (SAR). SAR studies suggested that phytotoxicity of sarmentine and its analogues was specific due to chemical structures, i.e., the analogues of the acid moiety of 1 were active, but the amine and its analogues were inactive; the ester analogues and amide analogues with a primary amine of 1 were also inactive. In addition, quantification of 1 from different resources of the dry P. longum fruits using liquid chromatography-mass spectrometry showed a wide variation, ranging from almost zero to 0.57%. This study suggests that 1 has potential as an active lead molecule for synthesized herbicides as well as for bioherbicides derived from natural resources.

Syntheses and herbicidal activity of new triazolopyrimidine-2-sulfonamides as acetohydroxyacid synthase inhibitor

The triazolopyrimidine-2-sulfonanilide, discovered from preparing bioisosteres of the sulfonylurea herbicides, is an important class of acetohydroxyacid synthase (AHAS, EC 4.1.3.18) inhibitors. At least over ten triazolopyrimidine sulfonanilides have been commercialized as herbicides for the control of broadleaf weeds and grass with cereal crop selectivity. Herein, a series of triazolopyrimidine-2-sulfonanilides were designed and synthesized with the aim of discovery of new herbicides with higher activity. The assay results of the inhibition activity of the synthesized compounds against Arabidopsis thatiana AHAS indicated that some compounds showed a little higher activity against flumetsulam (FS), the first commercial triazolopyrimidine-2-sulfonanilide-type herbicide. The ki values of two promising compounds 3d and 8h are respectively, 1.61 and 1.29μM, while that of FS is 1.85μM. Computational simulation results indicated the ester group of compound 3d formed hydrogen bonds with the surrounding residues Arg’198 and Ser653, which accounts for its 11.5-folds higher AHAS inhibition activity than Y6610. Further green house assay showed that compound 3d has comparable herbicidal activity as FS. Even at the concentration of 37.5g.ai/ha, 3d showed excellent herbicidal activity against Galium aparine, Cerastium arvense, Chenopodium album, Amaranthus retroflexus, and Rμmex acetasa, moderate herbicidal activity against Polygonum humifusum, Cyperus iria, and Eclipta prostrate. The combination of in vitro and in vivo assay indicated that 3d could be regarded as a new potential acetohydroxyacid synthase-inhibiting herbicide candidate for further study.

Evolving understanding of the evolution of herbicide resistance

A greater number of, and more varied, modes of resistance have evolved in weeds than in other pests because the usage of herbicides is far more extensive than the usage of other pesticides, and because weed seed output is so great. The discovery and development of selective herbicides are more problematic than those of insecticides and fungicides, as these must only differentiate between plant and insect or pathogen. Herbicides are typically selective between plants, meaning that before deployment there are already some crops possessing natural herbicide resistance that weeds could evolve. The concepts of the evolution of resistance and the mechanisms of delaying resistance have evolved as nature has continually evolved new types of resistance. Major gene target-site mutations were the first types to evolve, with initial consideration devoted mainly to them, but slowly 'creeping' resistance, gradually accruing increasing levels of resistance, has become a major force owing to an incremental accumulation of genetic changes in weed populations. Weeds have evolved mechanisms unknown even in antibiotic as well as other drug and pesticide resistances. It is even possible that cases of epigenetic 'remembered' resistances may have appeared.

Albucidin: a novel bleaching herbicide from Streptomyces albus subsp. chlorinus NRRL B-24108

A novel nucleoside phytotoxin, albucidin (1), was isolated from the culture broth of Streptomyces albus subsp. chlorinus NRRL B-24108 using bioassay directed fractionation. The structure of the new natural product, albucidin, was determined by NMR and MS; however, the compound has been reported earlier in the literature following synthetic modification of oxetanocin. This is the first report of herbicidal activity for compounds of this structural type. Albucidin shows high levels of broad spectrum activity following post-emergence applications as well as moderate levels of pre-emergence activity. Accordingly, albucidin could be an important new lead for herbicide discovery.

Penoxsulam—Structure–activity relationships of triazolopyrimidine sulfonamides

The discovery of the sulfonamide herbicides, which inhibit the enzyme acetolactate synthase (ALS), has resulted in many investigations to exploit their herbicidal activity. One area which proved particularly productive was the N-aryltriazolo[1,5- c]pyrimidine sulfonamides, providing three commercial herbicides, cloransulam-methyl, diclosulam and florasulam. Additional structure–activity investigations by reversing the sulfonamide linkage resulted in the discovery of triazolopyrimidine sulfonamides with cereal crop selectivity and high levels of grass and broadleaf weed control. Research efforts to exploit these high levels of weed activity ultimately led to the discovery of penoxsulam, a new herbicide developed for grass, sedge and broadleaf weed control in rice. Synthetic efforts and structure–activity relationships leading to the discovery of penoxsulam will be discussed.

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

ATP synthase, a double-motor enzyme, plays various roles in the cell, participating not only in ATP synthesis but in ATP hydrolysis-dependent processes and in the regulation of a proton gradient across some membrane-dependent systems. Recent studies of ATP synthase as a potential molecular target for the treatment of some human diseases have displayed promising results, and this enzyme is now emerging as an attractive molecular target for the development of new therapies for a variety of diseases. Significantly, ATP synthase, because of its complex structure, is inhibited by a number of different inhibitors and provides diverse possibilities in the development of new ATP synthase-directed agents. In this review, we classify over 250 natural and synthetic inhibitors of ATP synthase reported to date and present their inhibitory sites and their known or proposed modes of action. The rich source of ATP synthase inhibitors and their known or purported sites of action presented in this review should provide valuable insights into their applications as potential scaffolds for new therapeutics for human and animal diseases as well as for the discovery of new pesticides and herbicides to help protect the world's food supply. Finally, as ATP synthase is now known to consist of two unique nanomotors involved in making ATP from ADP and P(i), the information provided in this review may greatly assist those investigators entering the emerging field of nanotechnology.

The Challenges of Specialty Crop Weed Control, Future Directions

The process of labeling new herbicides for specialty crops has always been difficult. Progress in solving specialty crop weed control problems will likely be more challenging in the future. Major crops like corn, cotton, rice, soybean, and wheat are planted on millions of hectares, and most of these crops are treated with herbicides. In contrast, specialty crops (i.e., minor crops, e.g., container ornamentals or lettuce) are planted on 122,000 ha or less; thus, the potential value of herbicide sales is limited in these crops by the low number of hectares planted per crop. High crop value, small hectarage per crop, and generally marginal herbicide selectivity results in a high potential of liability for herbicide registrants and little incentive to label herbicides in these crops. The Interregional Project Number 4 (IR-4) program facilitates the registrations of pesticides on minor crops. Work needed to support pesticide tolerance in a given crop is conducted by IR-4 and cooperators. However, to develop new crop tolerances, the IR-4 process requires new herbicides. The success of glyphosate-resistant soybean has resulted in a less profitable herbicide market for all crops. In response, most primary pesticide manufacturers have reduced the size, or even eliminated herbicide discovery programs. As private industry slows or stops herbicide development, there will be fewer new minor-crop herbicides. Many questions face minor-crop weed scientists. For example, what are other practical solutions to control weeds in minor crops besides herbicides? Should research focus on development of competition models and decision thresholds or on weed removal tools such as robotics? What funding sources are available for minor-crop weed scientists? Are grant programs at the Federal level prepared to increase support for minor-crop weed research? Will university administrators replace retiring specialty crop weed scientists, knowing that their funding sources will produce little overhead? These questions require a response from all parties interested in specialty crop weed control.Nomenclature: Corn, Zea mays L., cotton, Gossypium hirsutum L., lettuce, Lactuca sativa L., rice, Oryza sativa L., soybean, Glycine max (L.) Merr.; wheat, Triticum aestivum L.

Suppression of CtpA in Mouseearcress Produces a Phytotoxic Effect: Validation of CtpA as a Target for Herbicide Development

To validate carboxyterminal processing protease of D1 protein (CtpA) as a target for herbicide discovery, CtpA sense mRNAs were overexpressed to suppress the internal level of CtpA protein in mouseearcress plants. Using antibodies raised against recombinant CtpA protein, we demonstrated that we have generated transgenic mouseearcress plants with reduced levels of CtpA protein and plants with elevated levels of CtpA protein. Transgenic plants with severely reduced levels of CtpA protein exhibited a bleached and chlorotic phenotype and stunted growth. The mutant phenotypes were enhanced by bright illumination. However, plants with a slight reduction of CtpA protein did not exhibit the mutant phenotype and could not be distinguished from wild-type plants under normal growth conditions. Several CtpA enzyme inhibitors were shown to have herbicidal activity in planta. Interestingly, plants producing excessive amount of CtpA protein were shown to be resistant to these inhibitors. Our results suggest that CtpA is essential for plant growth and development, but a reduced amount of CtpA is sufficient to carry out its essential function. CtpA may be a good target for herbicide development, but very high levels of inhibition may be required to produce a herbicidal effect. In addition, overexpressing CtpA in target plants might provide a mechanism for producing plants resistant to the herbicide.

Application of Cross‐Coupling and Metalation Chemistry of 3(2H)‐Pyridazinones to Fungicide and Herbicide Discovery

AbstractFor Abstract see ChemInform Abstract in Full Text.