Acaricide mode of action

The last few years have seen the introduction of an unprecedented number of new classes of acaricides with novel or under-exploited modes of action, discovered by traditional screening. Acaricide research has uncovered several unrelated compounds that possess improved properties. Pyridaben, acequinocyl, diafenthiuron, etoxazole, spirodiclofen and bifenazate, in particular, are acaricides that are safe to beneficials, have low mammalian toxicity and short environmental persistence. Many of the new acaricides appear to affect mitochondrial respiration, and previously unknown targets affecting mite growth and development have been identified, offering new opportunities for mite control.     

The biochemical mode of action of some modern anthelmintics

The possible biochemical modes of action of levamisole, morantel, benzimidazoles and salicylanilides are discussed. It is concluded that the modes of action of none of these anthelmintics is properly understood, but it seems likely that levamisole and pyrantel act on the nematode nervous system, benzimidazoles affect cellular integrity and the uncoupling properties of salicylanilides could enable them to act at several sites.     

The mode of action of the antifungal agent phosphite1

Field studies have established that phosphorous acid (phosphite) is an effective control against a number of plant diseases. However, the mechanism of control is not known. We have used Phytophthora palmiuora to investigate the action of phosphorous acid as an antifungal agent. Phosphite is toxic to Phytophthoru in uitro, but concentrations which completely inhibit growth in vitro are rarely ever achieved in phosphite-treated plants. Phosphite concentrations (1 m mol 1^-1) which do not inhibit fungal growth in vitro cause changes in the metabolism and cell-wall components. We suggest that phosphite, when present in plants in concentrations too low to control fungi in vitro, may cause modification of the fungal cell surface in such a way that the plant is able to recognize it as foreign and respond by normal defence mechanisms.     

Antifungal mode of action of triforine

Rapidly growing mycelia of Aspergillus fumigatus treated with 10 μg/ml triforine (N,N′-bis-(1-formamido-2,2,2-trichloroethyl)-piperazine) showed little or no inhibition in dry weight increase prior to 2 h. By 2.5–3 h, triforine inhibited dry weight increase by 85%. The effects of triforine on protein, DNA, and RNA syntheses corresponded to the effect on dry weight increase both in time of onset and magnitude. Neither glucose nor acetate oxidation were inhibited by triforine.Ergosterol synthesis was almost completely inhibited by triforine even in the first hour after treatment. Inhibition of ergosterol synthesis was accompanied by an accumulation of the ergosterol precursors 24-methylenedihydrolanosterol, obtusifoliol, and 14α-methyl-Δ^{8, 24 (28)}-ergostadienol. Mycelia treated with 5 μg/ml of triarimol (α-(2,4-dichlorophenyl)-α-phenyl-5-pyrimidinemethanol) also accumulated the same sterols as well as a fourth sterol believed to be Δ^{5, 7}-ergostadienol.Identification of 4,4-dimethyl-Δ^{8, 24 (28)}-ergostadienol in untreated mycelia indicates that the C-14 methyl group is the first methyl group removed in the biosynthesis of ergosterol by A. fumigatus. The lack of detectable quantities of 4,4-dimethyl-Δ^{8, 24 (28)}-ergostadienol in triforine or triarimol-treated mycelia and the accumulation of C-14 methylated sterols in treated mycelia suggests that both fungicides inhibit sterol C-14 demethylation. The accumulation of Δ^{5, 7}-ergostadienol in triarimol-treated mycelia further implies that triarimol also inhibits the introduction of the sterol C-22(23) double bond.Two strains of Cladosporium cucumerinum tolerant to triforine and triarimol were also tolerant to the fungicide S-1358 (N-3-pyridyl-S-n-butyl-S′-p-t-butylbenzyl imidodithiocarbonate).     

Studies of clomazone mode of action

Intact spinach chloroplasts were used to determine if clomazone, 5-OH clomazone, and/or 5-keto clomazone inhibited the chloroplastic isoprenoid pathway. When isopentenyl pyrophosphate was used as a precursor, neither clomazone nor the clomazone metabolites (5-OH clomazone and 5-keto clomazone) inhibited the formation of products separated by HPLC in the organic phase. However, when pyruvate, a substrate for the first committed step of the pathway, was used as a precursor, both 5-keto clomazone and fosmidomycin reduced the formation of a non-polar product and increased the formation of a polar product in the organic phase. Only 5-keto clomazone, not 5-OH clomazone or clomazone, inhibited the formation of an additional product other than fosmidomycin in the aqueous phase from pyruvate incorporation. In an in vitro assay, 5-keto clomazone inhibited DXP synthase, the enzyme catalyzing the first committed step of the chloroplastic isoprenoid pathway. Therefore, our studies show that neither clomazone nor 5-OH clomazone inhibits the chloroplastic isoprenoid pathway, only 5-keto clomazone does.     

Antifungal mode of action of imazalil

Imazalil had no effect on the initial growth of mycelia of Penicillium italicum (for 10 hr) or Aspergillus nidulans (for 2 hr). In P. italicum during this period neither respiration nor cell permeability was affected, but uptake of [³²P]phosphate, [¹⁴C]leucine, or [¹⁴C]uridine was partially inhibited. The initial (5 hr) inhibition of substrate uptake coincided with a 50% reduction in ergosterol content. Within 0.5 hr, incorporation of [¹⁴C]acetate into C-4-desmethyl sterols was strongly inhibited in mycelia of A. nidulans treated with 0.5 μg/ml of imazalil. However, radioactivity in C-4-methyl and dimethyl sterols exceeded that of control cultures. Concentrations of imazalil as low as 0.005 μg/ml caused short-term (1 hr) declines of incorporation into desmethyl sterols and increases into the C-4-methyl and dimethyl sterols. Incorporation into phospholipids, triglycerides, and free fatty acids was not affected. These data suggest that the primary antifungal action of imazalil is inhibition of demethylation in the biosynthesis of ergosterol.     

On the mode of action of prothiocarb

Prothiocarb, S-ethyl-N-(3-dimethy laminopropyl) thiocarbamic acid hydrochloride, a fungicide active against Oomycetes, possesses two modes of action. Its most common action is caused by the entire prothiocarb molecule. In this way it acts against Peronosporales like Pythium and Phytophthora, against Leptomitales like Apodachlya punctata and against part of the Saprolegniales like Aphanomyces species and Dictyuchus sterilis. For another part of the Sapro legniales, however, comprising Achlya radiosa, Pythiops is intermedia and Saprolegnia megasperma fungitoxicity must be ascribed to ethyl mercaptan released from prothiocarb.     

The mode of action of chlorsulfuron: A new herbicide for cereals

Chlorsulfuron (2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]benzenesul-fonamide) is the active ingredient in DuPont “Glean” Weed Killer (formerly DPX-4189), a new herbicide for weed control in small grains as well as other uses. Continuous growth measurements of chlorsulfuron-sensitive seedlings demonstrated that the herbicide inhibits growth within 2 hr of application and by 8 hr reduces growth by 80%. This reduction in growth was closely associated with an inhibition of plant cell division. No significant effects were observed on auxin-, cytokinin-, or gibberellin-induced cell expansion. Photosynthesis, respiration, RNA synthesis, and protein synthesis were also initially unaffected under conditions where plant cell division is strongly inhibited.     

Biochemical mode of action of the acaricide fenazaflor

The active ingredient of ‘Lovozal’ (fenazaflor) is hydrolysed in solution to 5,6-dichloro-2-trifluoromethyl-benzimidazole (DTFB). Rat liver mitochondria were uncoupled by fenazaflor after a lag phase, while uncoupling by DTFB was immediate, and a similar situation occurred with mitochondria isolated from Tetranychus telarius L. (This is the first report of isolation of mite mitochondria.) Since both compounds ultimately have the same uncoupling activity, it is likely that fenazaflor exerts its effect only after hydrolysis to DTFB. Living mites showed a stimulation of respiration of 70% on addition of either fenazaflor or DTFB before death occurred, suggesting that the acaricidal effect of fenazaflor is due to uncoupling of oxidative phosphorylation after hydrolysis to DTFB.     

On the antifungal mode of action of tridemorph

Tridemorph (2,6-dimethyl-N-tridecylmorpholine) was active against representative of nearly all taxonomic groups of fungi; gram-positive bacteria were also sensitive although gram-negative were not. Tridemorph, 3–10 μg/ml, inhibited the multiplication of sporidia of Ustilago maydis more strongly than the increase of dry weight. The treated sporidia appeared swollen, multicellular, and sometimes branched. Unsaturated lipophilic compounds like α-tocopherol and trilinolein alleviated the toxicity of tridemorph to Botrytis allii and U. maydis. Protein and RNA syntheses were inhibited slightly. DNA synthesis was rather strongly affected already after 2 hr. Lipid synthesis was first inhibited but later stimulated. At an early stage (2 hr) treated cells differed already from control cells by a higher content of free fatty acids. Tridemorph also inhibited sterol biosynthesis. The antimicrobial spectrum, the characteristic morphology of treated cells of U. maydis, the observations on cross-resistance, the alleviating effect of unsaturated lipophilic compounds, and the alterations in neutral lipid pattern suggest strong similarity of the mode of action of tridemorph with that of the known inhibitors of sterol biosynthesis.     

The herbicidal mode of action of R-40244 and its absorption by plants

The herbicide R-40244, 1-(m-trifluoromethylphenyl)-3-chloro-4-chloromethyl-2-pyrrolidinone, was studied to elucidate its action and absorption by corn (Zea mays L. DeKalb XL-45A) and other plant species. R-40244 readily induced lead chlorosis in susceptible plants at relatively low rates of application. The leaf chlorosis was found to be related to a reduction in chlorophyll and β-carotene content and an accumulation of the β-carotene precursor, phytoene. The phytotoxic action of R-40244 occurred only under light conditions. R-40244 was readily absorbed by plant roots and translocated to foliar tissues. There were no discernible differences in R-40244 absorption between proadleaf and grassy species. However, uptake studies with eight plant species indicated that foliar accumulation tended to occur in susceptible species and root accumulation predominated in tolerant species.     

The mode of action of chlorsulfuron: The lack of direct inhibition of plant DNA synthesis

Chlorsulfuron (2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]benzene-sulfonamide), the active ingredient in DuPont Glean Weed Killer, has been proposed to act by inhibiting plant cell division. In order to further define the mode of action of this new herbicide, studies were made of the effects of chlorsulfuron on processes associated with plant DNA synthesis. No inhibitory effects were observed on DNA synthesis in isolated plant nuclei, and the enzymes DNA polymerase and thymidine kinase. Nucleoside precursors of DNA were not effective in lessening chlorsulfuron inhibition of thymidine incorporation into DNA of corn root tips. These results indicate that chlorsulfuron does not inhibit plant cell division by a direct inhibition of DNA synthesis.     

On the mode of action of the fungicide etridiazole

Etridiazole (5-ethoxy-3(trichloromethyl)-1,2,4-thiadiazole) is a fungicide primarily effective against fungi of the Oomycete group. After addition of the compound to the medium, growth of Mucor mucedo was impaired almost immediately. Oxygen uptake of the mycelia decreased only slightly at growth-inhibiting concentrations. Respiration of isolated mitochondria of Mucor was inhibited about 50% by high concentrations of the fungicide, while the respiratory control quotient remained constant. In contrast, rat liver mitochondria were not very sensitive to etridiazole. Etridiazole stimulates the hydrolysis of membrane-bound phospholipids to free fatty acids and lysophosphatides in isolated mitochondria of Mucor. Procaine, a well-known inhibitor of phospholipases, acts as an antidote for etridiazole in growth tests as well as in the hydrolysis of phosphatidylcholine by isolated mitochondria. Calcium ions in millimolar concentrations act like procaine. Therefore, it was assumed that the fungistatic effect of etridiazole was mainly caused by an activation of phospholipases in the mitochondrial membranes. Moreover, under the influence of etridiazole, a lipid peroxidation of membranes is observed. Tocopherol acts as an antidote. This could be the primary toxic effect in the mechanism of action of this fungicide. The enzymes involved are not yet identified.     

Mitochondrial involvement in the mode of action of acifluorfen

The herbicidal action of acifluorfen {5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid} was studied with greened and expanded discs from cotyledons of cucumber (Cucumis sativus L.). Discs were floated on various treatment solutions for 20 hr in darkness before exposure to 400 μE m^?2 sec^?1 of white light. Herbicide damage, as measured by electrolyte leakage, began in the light after a 1- to 2-hr lag period. Cytochemical methods at the ultrastructural level indicated that acifluorfen caused marked increases in production of superoxide radical and hydrogen peroxide in the mitochondrion, but not in the plastid. The mitochondrial inhibitors antimycin A, rotenone, CCCP, and DNP antagonized the action of acifluorfen, lengthening the lag period and reducing the rate of electrolyte leakage. Ethanol, α-tocopherol, N-[2-(2-oxo-1-imidazolidinyl)ethyl]-N′-phenylurea, and copper-penicillin also lengthened the lag phase and slowed the rate of damage, indicating that acifluorfen damage involves toxic oxygen species. PS II-inhibiting levels of DCMU, atrazine, or bentazon did not affect acifluorfen-induced ion leakage. Yellow tissue produced by treatment with tentoxin was supersensitive to acifluorfen, but white tissue produced by treatment with norflurazon was relatively insensitive. These data indicate that, after an initial carotenoid-acifluorfen interaction, the mitochondrion is involved in production of toxic oxygen species and that this process is closely tied to the mechanism of action of this herbicide.     

The mode of action of glufosinate in algae: The role of uptake and nitrogen assimilation pathways

The purpose of this work was to investigate the in-vivo mode of action of glufosinate in comparison with that of the known glutamine synthetase inhibitor, methionine sulfoxmine, in photoautotrophic microorganisms. Using the eukaryotic green alga Chlorella fusca (Shih. & Krauss) and the cyanobacterium Anacystis nidulans (Kratz & Myers), currently developed [¹⁵N]NMR pulselabelling techniques have been employed to study the inhibition of ammonia assimilation. The results show that, while methionine sulfoximine immediately blocks glutamine synthesis, glufosinate action requires an induction process in both organisms investigated, possibly indicating the de-novo synthesis of an amino acid membrane carrier. In addition, the observed ability of C. fusca to incorporate nitrogen into glutamate under glutamine synthetase-inhibiting conditions is explicable by an anabolic function of a glutamate dehydrogenase in this organism. This might explain the large differences in observed species sensitivity to glufosinate exposure.     

The mode of action of RH‐1965: a new phenylpyrimidinone bleaching herbicide

RH‐1965 is a new bleaching herbicide which causes newly developing leaf tissue to emerge devoid of photosynthetic pigments. Mode‐of‐action studies revealed that RH‐1965 inhibited the accumulation of both total chlorophyll and β‐carotene. Concomitantly, it induced the accumulation of the β‐carotene precursors, phytoene, phytofluene and, in particular, ξ‐carotene. Inhibition of chlorophyll accumulation by RH‐1965 is attributed to the photo‐oxidative destruction of chlorophyll in the absence of β‐carotene because RH‐1965 blocked chlorophyll accumulation to a greater extent under high light (50–330 µE m⁻² s⁻¹) than under low light (0.8 µE m⁻² s⁻¹) conditions. Radish (Raphanus sativus L) and barnyardgrass (Echinochloa crus‐galli (L) Beauv) were very senstive to RH‐1965. Under high light (330 µE m⁻² s⁻¹), the I₅₀ values for inhibition of chlorophyll accumulation were 0.10 and 0.15 µM , respectively. Wheat (Triticum aestivus L), on the other hand, was much less sensitive to RH‐1965 (I₅₀ = 1.4 µM ). It is concluded that the mode of action of RH‐1965 involves the inhibition of ξ‐carotene desaturation. © 2000 Society of Chemical Industry     

On the mode of action of the organophosphorus fungicide Hinosan

Samenvatting In onderzoek naar werkingsmechanismen van fungicide organische fosforverbindingen werd aangetoond dat Hinosan bijPiricularia oryzae tussenprodukten van de chitinesynthese kan doen ophopen. Dit duidt op een beïnvloeding van de chitinesynthese. De verbinding heeft ook een effect op de permeabiliteit van de celwandmembraan. Waarschijnlijk is dit effect primair verantwoordelijk voor de fungitoxiciteit van Hinosan en moet de remming van de chitinesynthese als een indirect effect worden beschouwd.     

Oils for weed control: Uses and mode of action

The role of oils in herbicide treatments is reviewed, both in terms of their own intrinsic activity and of their enhancement of the performance of other herbicides. The phytotoxicity of oils can be related to their physical properties. Their efficacy as adjuvants can vary with the plant/pesticide combination involved, and differences may also be observed between oils of mineral and vegetable origin. The possible mechanisms involved in the enhancement of activity by oils are discussed and areas of work that might elucidate these fun her are indicated.