Pesticide effects on secondary metabolism of higher plants

Secondary compounds serve both endogenous and exogenous functions in higher plants because they are involved in plant growth and development as well as intraspecies and interspecies interactions. Documentation of the effects of pesticides on secondary compound biosynthesis in higher plants is increasing. While several herbicides have been reported to reduce levels of secondary compounds by non-specific mechanisms, a few herbicides, such as alachlor and glyphosate, directly affect specific biosynthetic steps. Alachlor reduces flavonoid synthesis at a step late in the biosynthetic pathway, and glyphosate blocks synthesis of all cinnamate derivatives by inhibiting 5-enolpyruvyl shikimate-3-phosphate (EPSP) synthase. Inhibition of EPSP synthase also leads to the accumulation of high levels of shikimate, benzoic acids and benzoic acid derivatives. The sulfonylureas and p-nitro-substituted diphenylether (DPE) herbicides can cause increases in the level of cinnamatederived phenolic compounds and the DPEs can cause dramatic increases in terpenoid stress metabolites. Certain fungicides are thought to act through enhancing the capacity of plants to produce phytoalexins. These and other data suggest that sublethal effects of pesticides on target and non-target plants can significantly affect agricultural ecosystems by altering the synthesis of compounds important in inter- and intraspecies interactions.     

Natural products as sources of herbicides: current status and future trends

Although natural product-based discovery strategies have not been as successful for herbicides as for other pesticides or pharmaceuticals, there have been some notable successes. Phosphinothricin, the biosynthetic version of glufosinate, and bialaphos are phytotoxic microbial products that have yielded commercial herbicides. Cinmethylin, a herbicidal analogue of cineole, has been sold in Europe and Asia. The triketone herbicides are derivatives of the plant-produced phytotoxin leptospermone. These products represent only a small fraction of commercialized herbicides, but they have each introduced a novel molecular target site for herbicides. Analysis of the literature reveals that phytotoxic natural products act on a large number of unexploited herbicide target sites. The pesticide industry's natural product discovery efforts have so far concentrated on microbially derived phytotoxins, primarily from non-pathogenic soil microbes, involving the screening of large numbers of exotic isolates. Plant pathogens usually produce potent phytotoxins, yet they have received relatively little attention. Even less effort has been made to discover plant-derived phytotoxins. Bioassay-directed isolation has been the preferred method of discovery after a producing organism is selected. This laborious approach often leads to rediscovery of known compounds. Modern tandem separation/chemical characterization instrumentation can eliminate much of this problem by identification of compounds before they are bioassayed.     

Transformation rates of ortho-substituted thiophene and benzene carboxylic esters: Application to thifensulfuron-methyl and metsulfuron-methyl herbicides

The rate constants for soil degradation and alkaline hydrolysis of two herbicides, metsulfuron-methyl and thifensulfuron-methyl, have been determined. In order to explain the difference in behaviour of the two compounds, the chemical and enzymatic hydrolysis of some ortho-substituted methyl benzoates and methyl 3-substituted thiophene-2-carboxylates were studied. The data are consistent with a difference in polar and steric effects of the substituents in benzene and thiophene derivatives.     

The herbicidal activity of 2-alkyl-2-cyanoacetanilides

The pre-emergent herbicidal activity of 2-alkyl-2-cyanoacetanilide derivatives (a new class of anilide herbicides) is reported and the relationship between structure and activity examined. The compounds appear to act by inhibiting development of root growth. Comparisons with 2-chloroacetanilide herbicides reveal similarities and differences which suggest that, whilst both groups may interact at a similar cellular site, a different reaction mechanism may be involved.     

Synthesis and plant growth regulating properties of derivatives of alkyl 3-benzoyl-3-(3-chloro-4-substituted phenyl)-2-methylcarbazates

Alkyl 3-benzoyl-3-(3-chloro-4-substituted-phenyl)-2-methylcarbazates (isoelectronic analogues of wild oat herbicides) have plant growth regulating properties for various weeds and crops. Some derivatives of carbazates, bearing halogen in the 4-position of the phenyl group, have been shown to have the highest activity of the prepared compounds.     

Studies on the effect of different cyclohexane-1,3-diones on de-novo fatty acid biosynthesis in poaceae

Cyclohexane-1,3-diones such as the herbicides cycloxydim, sethoxydim, alloxydim and clethodim are known to be specific inhibitors of the plastid-located acetyl-CoA carboxylase (ACCase) in Poaceae, a key enzyme of de-novo fatty acid biosynthesis in higher plants. Using several new cyclohexane-1,3-dione derivatives and known herbicides, the relationships between chemical structure and enzyme inhibition have been studied. The basic cyclohexane-1,3-dione structure was modified at three different positions. These compounds were tested for inhibition of the de novo fatty-acid biosynthesis in test systems of etioplasts isolated from Avena sativa L. and Hordeum vulgare L. seedlings and also for inhibition of the isolated barley ACCase. The I₅₀ values of these cyclohexane-1,3-diones were determined. The influence of the modification of alkyl chains (length and type of substituent) on the degree of ACCase-inhibition is discussed. Several new compounds were found that were about two orders more active than the known herbicides cycloxydim or sethoxydim in the etioplast and ACCase test systems but not necessarily on the level of whole plants.     

Recent advances in allelopathy for weed control: from knowledge to applications

Allelopathy is the biological phenomenon of chemical interactions between living organisms in the ecosystem, and must be taken into account in addressing pest and weed problems in future sustainable agriculture. Allelopathy is a multidisciplinary science, but in some cases, aspects of its chemistry are overlooked, despite the need for a deep knowledge of the chemical structural characteristics of allelochemicals to facilitate the design of new herbicides. This review is focused on the most important advances in allelopathy, paying particular attention to the design and development of phenolic compounds, terpenoids and alkaloids as herbicides. The isolation of allelochemicals is mainly addressed, but other aspects such as the analysis and activities of derivatives or analogs are also covered. Furthermore, the use of allelopathy in the fight against parasitic plants is included. The past 12 years have been a prolific period for publications on allelopathy. This critical review discusses future research areas in this field and the state of the art is analyzed from the chemist's perspective. © 2019 Society of Chemical Industry     

An evaluation of the herbicidal and plant growth regulatory activity of a novel class of carbohydrate-derived 6,8-dioxabicyclo[3.2.1]octanes

Thirty-five carbohydrate-derived dioxabicyclo[3.2.l]octane derivatives have been tested for herbicidal and plant growth regulatory (PGR) activity in an Arabidopsis thaliana assay. Nine of these were herbicidal at concentrations of ? 16 μg ml^?1 in the growth medium. Three compounds, viz, 1,6-anhydro-3-deoxy-4-O-(2,6-dichlorobenzyl)-2-O-methyl-β-D-ribo-hexopyranose(I), its 4-O-benzyl analogue (II), and l,6-anhydro-2-azido-4-O-benzyl-2,3-dideoxy-β-D-ribo-hexopyranose (III) were very active herbicides, killing plants by the rosette stage at 1 μg ml^?1 or less. At lower rates, the herbicides acted as growth regulators, reducing growth rates of shoots and roots as well as flowering and seed-pod development. A further 14 compounds exerted PGR effects only, while 12 compounds were virtually inactive at 16 μg ml^?1, the highest rate tested. The ability of the active compounds to reduce seed viability on mature plants at sublethal concentrations was demonstrated in four cases.     

United States Department of Agriculture-Agricultural Research Service research on natural products for pest management

Recent research of the Agricultural Research Service of USDA on the use of natural products to manage pests is summarized. Studies of the use of both phytochemicals and diatomaceous earth to manage insect pests are discussed. Chemically characterized compounds, such as a saponin from pepper (Capsicum frutescens L), benzaldehyde, chitosan and 2-deoxy-D-glucose are being studied as natural fungicides. Resin glycosides for pathogen resistance in sweet potato and residues of semi-tropical leguminous plants for nematode control are also under investigation. Bioassay-guided isolation of compounds with potential use as herbicides or herbicide leads is underway at several locations. New natural phytotoxin molecular target sites (asparagine synthetase and fructose-1,6-bisphosphate aldolase) have been discovered. Weed control in sweet potato and rice by allelopathy is under investigation. Molecular approaches to enhance allelopathy in sorghum are also being undertaken. The genes for polyketide synthases involved in production of pesticidal polyketide compounds in fungi are found to provide clues for pesticide discovery. Gene expression profiles in response to fungicides and herbicides are being generated as tools to understand more fully the mode of action and to rapidly determine the molecular target site of new, natural fungicides and herbicides.     

4-取代嘧啶基苯磺酰脲类化合物的合成与除草活性

为了探寻磺酰脲类除草剂的构效关系,以单嘧磺隆和单嘧磺酯为先导化合物,在嘧啶环上引入取代苯基,设计合成了16个新型单取代嘧啶磺酰脲衍生物,其结构均经过核磁共振氢谱、质谱和元素分析确证。盆栽试验结果表明:在1.5 kg/hm2时,大部分化合物对供试杂草具有一定的抑制活性,其中对双子叶杂草的活性高于对单子叶杂草的活性,但均不及先导化合物的活性。     

Synthesis and Evaluation of New Ethyl 2,3- Dihydro-3-oxoisothiazolo[5,4-b]pyridine- 2-alkanoate Derivatives as Potential Herbicides

Several ethyl 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridine-2-alkanoate derivatives were synthesized as herbicides. Only 5-methyl derivatives inhibited both hypocotyl and root growth in the lettuce (Lactuca sativa L.) seedling test at 100 mg litre^-1. Only ethyl propionate and valerate derivatives showed significant inhibition at 0·1 mg litre^-1, whereas ethyl acetate or butyrate derivatives were inactive. Contrary to unoxidized derivatives, the inhibitory effect of 1-oxide and 1,1-dioxide derivatives was strongly dependent on concentration; ethyl 2,3-dihydro-5-methyl-3-oxoisothiazolo[5,4-b]pyridine-2-propionate 1,1-dioxide inhibited 100% of germination at 100 mg litre^-1 and 45% of lettuce seedling growth at 0·1 mg litre^-1. Quantitative structure–inhibition of growth relationship analysis carried out by adaptive least-squares (ALS) method gave a good correlation with small and hydrophobic 5-substituents as well as with odd carbon-chain ethyl alkanoates in position 2. Active compounds did not show auxin-like activity from 0·1 to 100 mg litre^-1. © 1997 SCI.     

Auxin herbicides: current status of mechanism and mode of action

Synthetic compounds that act like phytohormonal ‘superauxins’ have been among the most successful herbicides used in agriculture for more than 60 years. These so‐called auxin herbicides are more stable in planta than the main natural auxin, indole‐3‐acetic acid (IAA), and show systemic mobility and selective action, preferentially against dicot weeds in cereal crops. They belong to different chemical classes, which include phenoxycarboxylic acids, benzoic acids, pyridinecarboxylic acids, aromatic carboxymethyl derivatives and quinolinecarboxylic acids. The recent identification of receptors for auxin perception and the discovery of a new hormone interaction in signalling between auxin, ethylene and the upregulation of abscisic acid biosynthesis account for a large part of the repertoire of auxin‐herbicide‐mediated responses, which include growth inhibition, senescence and tissue decay in sensitive dicots. An additional phenomenon is caused by the quinolinecarboxylic acid quinclorac, which also controls grass weeds. Here, the accumulation of phytotoxic levels of tissue cyanide, derived ultimately from quinclorac‐stimulated ethylene biosynthesis, plays a key role in eliciting the herbicidal symptoms in sensitive grasses. Copyright © 2009 Society of Chemical Industry     

The herbicidal activity of 3-substituted 1-phenylureas

A variety of 1-phenylureas, substituted in the 3-position with one acyl, alkoxycarbonyl or cyano group, and optionally with a lower alkyl group, have been synthesised and assessed for pre- and post-emergence herbicidal activity against a range of monocotyledonous and dicotyledonous weed species. Generally, activity was associated only with compounds containing two small substituents in the 3-position. Their possible metabolic fate is discussed in the light of comparisons with the activity of the commercial herbicides, fenuron, monuron and diuron, and their de-methylated derivatives.     

Rice paddy field herbicides and their effects on the environment and ecosystems

Paddy herbicides contribute to the reduction of weeding labor, however, there are concerns about their effects on the environment and ecosystems. The environmental burden of applied herbicides is heaviest in water systems such as irrigation channels and rivers. Herbicides are generally detected in rivers in concentrations in levels of ng/L for only 2 to 3 months after use. It is to be regretted that herbicides have been implicated in accidents involving fish, the impeded propagation of algae and other non‐target organisms. Therefore, it is necessary to assess the ecological risk, and the Environment Agency in Japan compiled an interim report on how pesticides' ecological effects should be assessed. Pesticides are separately examined for their toxicity (hazard assessment) and exposure (exposure analysis). However, to the environment and ecosystems there are many problems in assessing the ecological risk of pesticides, such as selection of geographic locations, methodology of assessing the impacts on ecosystems and monitoring the effect of pesticides. New herbicides are expected to have high selectivity and low toxicity. Decreasing herbicide toxicity requires high selectivity to distinguish target weeds from crops and non‐target organisms. New groups of compounds will be developed based on a biorational approach. Moreover, it is necessary to develop an environmentally low‐impact application method such as the use of granular types and sustained‐release formulation among others. It is important that integrated methods be used to control paddy weeds by combining ecological/agronomical, mechanical and biological control methods, instead of relying solely on chemical herbicides.     

Action mechanisms of acetolactate synthase-inhibiting herbicides

Herbicides that target the acetolactate synthase (ALS) are among the most widely used weed control chemicals since their introduction into the marketplace in the early 1980s, including five classes (sulfonylureas, imidazolinones, triazolopyrimidines, pyrimidinylthio (or oxy)-benzoates and sulfonylamino-carbonyltriazolinones). The mechanism researches have progressed unprecedentedly in the last two decades. Primary mode of action of the ALS-inhibiting herbicides that interfere with the activity of ALS enzyme seems no longer in doubt. Three lines of investigation from physiology, genetics, molecular and chemical structure aspects came together to prove that ALS is the site of action. Researches on the effects of branched chain amino acids (BCAAs) synthesis or protein metabolism caused by ALS-inhibiting herbicide elicit lots of disputations. Besides these two main works, other secondary effects of ALS inhibition, such as buildup of 2-ketobutyrate (α-ketobutyrate or 2-KB) or 2-aminobutyrate (2-AB, the transamination product of 2-KB), depletion of intermediates of the pathway for some critical processes, disruption of photosynthesis transport and respiration system etc., have also been implicated in the mechanism of plant death. However, there are still some disputations and doubts on the precise mechanisms that need further probing into. Further more, as many ALS-inhibiting herbicides and their derivatives are chiral with one or even more enantiomers, which may behave quite differently in biochemical processes, the effects and the environmental fate of chiral herbicides need to be investigated stereospecifically. By this, we can have a better understanding about the herbicides and avoid unnecessary pollution load.     

Pathogens and their products affecting weedy plants

There are many natural enemies of weedy plants; among them are plant pathogens. Plant pathogens are capable of affecting plants, in part because of the phytotoxins they produce. Phytoloxins of weedy pathogens are produced in culture media by most of the phytopathogenic fungi of weeds that we have studied. In most cases the phytotoxin(s) usually belongs to a family of related compounds produced by the pathogen. Phytotoxin production in the medium can be optimized by placement of the host extract into the medium. Lethal activity is usually observed in the concentration range of 10^-3-10^-6M. The concept of using these molecules, or derivatives thereof, or related compounds as herbicides, should be explored.     

吡啶衍生物研究(IX):N-(1-甲氧羰基)乙基-N-[5-(2-氯吡啶-4-基)-1,3,4-噻二唑-2-基]酰胺的合成及除草活性

为了进一步研究前期发现的除草先导化合物2-仲丁氨基-5-(2-氯吡啶-4-基)-1，3，4-噻二唑(BCPT)的结构-活性关系并提高其除草活性，设计并合成了一系列N-(1-甲氧羰基)乙基-N-[5-(2-氯吡啶-4-基)-1，3，4-噻二唑-2-基]酰胺类化合物。其苗后除草活性测定结果表明，所有化合物的活性都远低于BCPT本身。说明BCPT可能具有与传统酰胺类除草剂不同的作用机制。     

Mode of action,crop selectivity,and soil relations of the sulfonylurea herbicides

The sulfonylurea herbicides are characterized by broad-spectrum weed control at very low use rates (c. 2–75 g ha^?1), good crop selectivity, and very low acute and chronic animal toxicity. This class of herbicides acts through inhibition of acetolactate synthase (EC 4.1.3.18; also known as acetohydroxyacid synthase), thereby blocking the biosynthesis of the branched-chain amino acids valine, leucine and isoleucine. This inhibition leads to the rapid cessation of plant cell division and growth. Crop-selective sulfonylurea herbicides have been commercialized for use in wheat, barley, rice, corn, soybeans and oilseed rape, with additional crop-selective compounds in cotton, potatoes, and sugarbeet having been noted. Crop selectivity results from rapid metabolic inactivation of the herbicide in the tolerant crop. Under growth-room conditions, metabolic half-lives in tolerant crop plants range from 1–5 h, while sensitive plant species metabolize these herbicides much more slowly, with half-lives > 20 h. Pathways by which sulfonylurea herbicides are inactivated among these plants include aryl and aliphatic hydroxylation followed by glucose conjugation, sulfonylurea bridge hydrolysis and sulfonamide bond cleavage, oxidative O-demethylation and direct conjugation with (homo)glutathione. Sulfonylurea herbicides degrade in soil through a combination of bridge hydrolysis and microbial degradation. Hydrolysis is significantly faster under acidic (pH 5) than alkaline (pH 8) conditions, allowing the use of soil pH as a predictor of soil residual activity. Chemical and microbial processes combine to give typical field dissipation half-lives of 1–6 weeks, depending on the soil type, location and compound. Very short residual sulfonylurea herbicides with enhanced susceptibility to hydrolysis (DPX-L5300) and microbial degradation (thifensulfuron-methyl) have been developed.     

Comparison of physiological effects of fluazifop-butyl and sethoxydim on oat (Avena sativa L.)

Laboratory experiments were conducted to compare the physiological effects of two herbicides: fluazifop-butyl {butyl ( RS )-2-[4-(5-trifluoromethyl-2-pyridyloxy)phenoxy]-propionate} and sethoxydim {(±)-2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one} on oat ( Avena sativa L. cv. Zenshin). The herbicides strongly inhibited growth of oat and induced chlorosis at the basal part of shoots and ethylene production from the seedlings. The phytotoxicity of these herbicides in oat seedlings was alleviated by 2,4-D (2,4-dichlorophenoxyacetic acid), but not by IAA (indole-3-acetic acid). Coleoptile elongation induced by 2,4-D or IAA was inhibited by fluazifop-butyl and sethoxydim, suggesting both herbicides possess the activity to inhibit this auxin action. Fluazifop (free acid) and sethoxydim inhibited proton excretion from oat roots but fluazifop-butyl did not. This proton excretion was not restored by 2,4-D or IAA. Furthermore, cellular electrolyte leakage in oat shoots was increased by both herbicides, indicating that the membrane permeability was increased. We conclude that fluazifop-butyl and sethoxydim may have the same mechanism of action which leads to disruption of membrane integrity, although fluazifop-butyl acts as a free acid after hydrolysis (fluazifop).     

Synthesis, Properties, and Use of Copper-Chelating Amphiphilic Dithiocarbamates as Synergists of Oxidant-Generating Herbicides

The effect of herbicides that act by generating active oxygen species is often mitigated by the enzymes of the Halliwell-Asada oxygen detoxification pathway. Use of compounds interfering with this pathway synergizes herbicides, allowing the killing of weeds at lower herbicide doses. We have used different dithiocarbamate chelators (Dtcs) capable of removing copper from superoxide dismutase, the first enzyme of the pathway, suppressing its action. Dtcs with different hydrophilic-lipophilic properties (sodium salts of ethyl (2-(2-ethoxyethoxy)ethyl)-, butyl (2-(2-ethoxyethoxy)ethyl) -, hexyl (2-(2- ethoxyethoxy)ethyl)-, and dibutyldithiocarbamic acids) were synthesized so that they might penetrate plant cuticles better than sodium diethyldithiocarbamate. Octanol-water distribution ratios and the stabilities of their copper complexes were determined. All Dtcs tested had a high affinity for copper. The Dtcs did not prevent iron-catalyzed Fenton reaction leading to hydroxyl radical productionin vitro. Therefore they would not protect plants from the oxidative damage caused by herbicide, as do compounds that complex iron and thereby prevent the phytotoxic iron-catalyzed Fenton reaction. These amphiphilic compounds show some synergistic activityin vivo, with paraquat as well as lactofen, herbicides that generate active oxygen species by different mechanisms. The results demonstrate that dithiocarbamates have potential as synergists for oxidant-generating herbicides.