The interaction of folpet with the glutathione-dependent demethylation enzyme system of rat liver

The interaction of folpet with the glutathione-dependent enzyme demethylation of fenitrothion was studied. In a reaction catalyzed by methyltransferase from rat liver in the presence of 0.3 μmol of glutathione, 0.21 μmol of folpet caused a 100% inhibition of the demethylation of 0.2 μmol of fenitrothion. A parallel study was made on the qualitative and quantitative course of the reaction between folpet and glutathione. Phthalimide was formed as the main degradation product of folpet, but the composition of the degradation products of glutathione was dependent on the molar ratio of the reactants. Compounds absorbing at 267 nm (probably derivatives of 2-thiazolidinethiones) were formed when the ratio of glutathione to folpet was 4.5:1. When this ratio was reversed, oxidized glutathione was the main product. From observations on the course of the enzymatic demethylation of fenitrothion and on the degradation of folpet by glutathione, it appears that in the enzyme demethylation system, the reaction between fungicide and glutathione predominates.     

A mutant of Ustilago maydis deficient in sterol C-14 demethylation: Characteristics and sensitivity to inhibitors of ergosterol biosynthesis

An ergosterol-deficient mutant of Ustilago maydis was compared to the wild type in regard to morphology, growth rate, lipid content, and sensitivity to ergosterol biosynthetic inhibitors. Morphology of mutant sporidia is abnormal and resembles that of fenarimol-treated wild-type sporidia. Doubling time of mutant sporidia is 6.3 hr compared to 2.5 hr for the wild type. The mutant produces 24-methylenedihydrolanosterol, obtusifoliol, and 14α-methylfecosterol; ergosterol is absent. The sterols of the mutant are the same as those which accumulate in wild-type sporidia treated with the sterol C-14 demethylation inhibitors fenarimol, etaconazole, and miconazole. The level of free fatty acids is higher in the mutant than in wild-type cells. Growth of mutant sporidia is not inhibited by fenarimol, etaconazole, and miconazole, or by the sterol Δ¹⁴-reductase inhibitor azasterol A25822B at low concentrations which inhibit growth of wild-type sporidia. The residual growth rate of wild-type sporidia treated with low concentrations of the sterol C-14 demethylation inhibitors is about the same as that of untreated mutant sporidia. Therefore, the mutant would not be recognized as resistant in a wild-type population. The mutant is deficient in sterol C-14 demethylation and is similar in all properties studied to wild-type sporidia treated with sterol C-14 demethylation inhibitors. These findings support the contention that inhibition of sterol C-14 demethylation in U. maydis is the primary mode of toxicity of fenarimol, etaconazole, and miconazole. A secondary mode of toxicity is evident for miconazole and etaconazole at higher concentrations but is doubtful for fenarimol.     

Resistance in mutagen-induced mutants of Ustilago maydis to fungicides which inhibit ergosterol biosynthesis

Resistance to a number of inhibitors of sterol C-14 demethylation, (clotrimazole, imazalil, miconazole, fenarimol, nuarimol and triadimefon), as well as resistance to inhibitors of sterol C-14(15) double bond reduction, (tridemorph and fenpropi-morph), was readily induced in Ustilago maydis. Resistant mutants were obtained after mutagenic treatment by ultraviolet irradiation, or by treatment with 1-methyl-3-nitro-1-nitrosoguanidine, of sporidia of the wild-type strain, followed by selection in the presence of the toxicant. The level of resistance of these mutants varied appreciably. Although not always reciprocal, cross-resistance to fungicides which inhibit ergosterol biosynthesis (EBIs) appeared to be present in most cases. Several of the U. maydis mutants which were resistant to inhibitors of sterol C-14 demethylation lacked cross-resistance to tridemorph and fenpropimorph, or displayed increased sensitivity to fenpropimorph (negatively correlated cross-resistance). Cross-resistance between EBIs and the antimicrobial agents climbazole and lombazole was also established. It is suggested that fungal mutants that possess a resistance mechanism based on a deficiency in sterol C-14 demethylation or sterol C-14(15) double bond reduction, have a greatly reduced chance of survival.     

黄顶菊种子萌发过程中DNA甲基化的MSAP分析

为明确入侵植物黄顶菊Flaveria bidentis生长发育与DNA甲基化之间的相互关系,采用甲基化敏感扩增多态性(methylation sensitive amplification polymorphism,MSAP)方法研究了黄顶菊种子萌发过程中DNA甲基化的动态变化。结果表明,DNA甲基化与去甲基化两者共同调控黄顶菊生命初期的生长发育,且去甲基化的变化在种子萌发过程中占主导。筛选出的12对引物共扩增出998条MSAP条带,其中多态性条带为951条,多态性百分比为95.37%。黄顶菊种子萌发过程中胞嘧啶发生甲基化主要以双链甲基化形式为主,位点数为94个,而单链甲基化位点数仅为50个;多态性位点数占总位点数比率为48.95%,表明有近一半的位点发生了DNA甲基化和去甲基化的变化;发生去甲基化变化的多态性片段有73个,而发生甲基化变化的有21个,说明黄顶菊种子萌发阶段DNA甲基化的变化主要以去甲基化形式为主,且在萌发第4天后去甲基化数目持续快速上升。     

楝酰胺(rocaglamide)全合成研究进展

综述了迄今为止文献报道的楝酰胺(rocaglamide, 1 )的全合成方法,并对每一方法反应过程中的立体化学问题作了全面分析。     

Fungitoxicity and growth regulation involving aspects of lipid biosynthesis

Triarimol and triforine inhibit ergosterol biosynthesis in fungi and cause accumulation of free fatty acids, 24-methylenedihydrolanosterol, obtusifoliol and 14α-methyl-δ^8,24(28)-ergostadienol. Triparanol also inhibits ergosterol synthesis and causes accumulation of free fatty acids, but not of the latter 3 sterols. Triparanol appears to inhibit prior to lanosterol in the sterol biosynthetic pathway of Ustilago maydis and at unidentified sites subsequent to lanosterol which lead to the accumulation of a sterol which migrates with desmethylsterols on TLC plates. Quantitative abnormalities in sterols and free fatty acids in U. maydis are not produced by the fungicides carbendazim, chloroneb, carboxin and cycloheximide. A deficiency in nitrogen leads to a marked increase in triglycerides, but a normal distribution pattern for other lipids.Inhibition of oxidative demethylation of the sterol 14α-methyl group is probably the prime mechanism of inhibition of ergosterol biosynthesis by triarimol. Rates of formation of obtusifoliol and 14α-methyl-δ^8,24(28)-ergostadienol in triarimol-treated U. maydis cells suggest that C-4 demethylation occurs along an abnormal pathway which operates effectively only at high substrate concentrations. The growth retardant action of triarimol and ancymidol in higher plants most likely results from inhibition of a reaction in the gibberellin biosynthetic pathway analogous to sterol C-14 demethylation.Free fatty acid accumulation in U. maydis cells treated with inhibitors of sterol synthesis are derived mainly from polar lipid degradation and from de novo synthesis as a consequence of the disproportionality between fatty acid synthesis and utilization. The free fatty acids may play a significant role in the lethality of these inhibitors in this organism.     

Photolysis,metabolism and other factors influencing the performance of triadimefon as a powdery mildew fungicide

Triadimefon, 1-(4-chlorophenoxy)-3,3-dimethyl-1-( 1,2,4-triazol-1-yl)butanone, applied at low dosage rates to leaves of marrow, apple or barley plants gave effective control of the appropriate powdery mildew fungi. The compound appeared to be systemic and to have considerable vapour-phase activity. In marrow plants, up to 56% of triadimefon was metabolised to a mixture of two corresponding diastereoisomeric secondary alcohols. The mixture was identical with that obtained by chemical reduction of triadimefon. This mixture was also a very effective systemic fungicide and active in the vapour-phase. Triadimefon was also reduced when incubated with Aspergillus niger but this was important only in shake culture. In replacement culture experiments, mycelial mats of this fungus converted the compound into a different metabolite, its isopropyl analogue. This may have resulted from participation of triadimefon in the C-4 demethylation processes involved in fungal biosynthesis of ergosterol. Photolysis caused cleavage of the C-1 to triazole bond liberating 1,2,4-triazole, 4-chlorophenol and 4-chlorophenyl methyl carbonate, all of which were non-fungitoxic. The importance of this photolysis in the in-vivo situation is discussed.     

Photolytic demethylation of monuron and demethylmonuron in aqueous solution

Photochemical demethylation of monuron [3-(4-chlorophenyl)-1, 1-dimethylurea] and of demethylmonuron [ 1-(4-chlorophenyl)-3-methylurea] in aqueous solution was investigated. The photoproducts identified in this study were formaldehyde, formic acid and carbon dioxide. These products indicate that demethylation occurs either by oxidation of a methyl group to hydroxymethyl which is readily cleaved to yield formaldehyde, or by further oxidation to an N-formyl group, which is slowly hydrolysed under weakly acidic conditions to yield formic acid. Samples equilibrated either with air or oxygen (> 99 % purity) gave essentially the same yield of oxidation products. Experimental evidence indicated that extensive photodegradation of formaldehyde was occurring during photolysis, causing low recoveries of formaldehyde. Consequently, with [²H₃-methyl]demethylmonuron and deuterated water, only steady state concentrations of formaldehyde could be measured in an isotopic study.     

Resistance to inhibitors of sterol biosynthesis in field isolates or laboratory strains of the eyespot pathogen Pseudocercosporella herpotrichoides

Strains of Pseudocercosporella herpotrichoides collected in France on winter wheat give either fast-growing mycelial colonies with regular margins or slow-growing mycelial colonies with irregular margins. Most of the fastgrowing isolates were sensitive to triadimenol (EC₅₀ below 2mg litre^?1), but some of them were resistant to this inhibitor of sterol C-14 demethylation. In contrast, all the slow-growing strains were highly resistant to triadimenol (EC₅₀ greater than 100 mg litre^?1). This resistance was also expressed in inhibition of germ-tube elongation. Positive cross-resistance was observed between most of the inhibitors of sterol C-14 demethylation, with the exception of some imidazole derivatives (clotrimazole, prochloraz). All the fast-growing strains were tolerant to fenpropimorph and fenpropidin whereas the slow-growing ones were susceptible; the reverse was true with piperalin and tridemorph. All the field isolates were inhibited to the same extent by the inhibitors of squalene-epoxidase, nafifine and terbinafine. Two types of mutant resistant to triadimenol have been induced under laboratory conditions from sensitive fast-growing strains. The most common mutants were resistant to all the inhibitors of sterol C–14 demethylation and also in some conditions to fenpropimorph, tridemorph and the inhibitors of squalene-epoxidase. The other mutants were characterised by a reduced spectrum of cross-resistance between triadimenol and the other inhibitors of sterol biosynthesis. The field isolates and laboratory mutants resistant to triadimenol and propiconazole were also resistant to each of the four enantiomers of these two fungicides.     

A reassessment of the risk of rust fungi developing resistance to fungicides

Rust fungi are major pathogens of many annual and perennial crops. Crop protection is largely based on genetic and chemical control. Fungicide resistance is a significant issue that has affected many crop pathogens. Some pathogens have rapidly developed resistance and hence are regarded as high‐risk species. Rust fungi have been classified as being low risk, in spite of sharing many relevant features with high‐risk pathogens. An examination of the evidence suggests that rust fungi may be wrongly classified as low risk. Of the nine classes of fungicide to which resistance has developed, six are inactive against rusts. The three remaining classes are quinone outside inhibitors (QoIs), demethylation inhibitors (DMIs) and succinate dehydrogenase inhibitors (SDHIs). QoIs have been protected by a recently discovered intron that renders resistant mutants unviable. Low levels of resistance have developed to DMIs, but with limited field significance. Older SDHI fungicides were inactive against rusts. Some of the SDHIs introduced since 2003 are active against rusts, so it may be that insufficient time has elapsed for resistance to develop, especially as SDHIs are generally sold in mixtures with other actives. It would therefore seem prudent to increase the level of vigilance for possible cases of resistance to established and new fungicides in rusts. © 2014 Society of Chemical Industry     

Phenotypic instability of flusilazole sensitivity in Venturia inaequalis

Sensitivities of 16 monoconidial isolates of Venturia inaequalis to the sterol demethylation inhibitor flusilazole were found to be stable, when cultures which had been successively transferred to inhibitor-free nutrient agar and maintained at 20 C were retested 6 months after isolation. In contrast, with storage of these isolates at 2 C for 7 additional months, phenotypic sensitivities were subject to change. A high degree of phenotypic instability was also observed for 77 representative strains which had been subcultured for 10 months. In both cases, the majority of strains became more sensitive to flusilazole. The frequency and magnitude of these changes were most pronounced for strains with moderate levels of resistance. More than 70% of the strains investigated were collected from wild-type populations, suggesting that the reversion of resistant strains was not related to a process of unstable adaptation but to a high degree of plasticity in the genetic control of sensitivities to sterol demethylation inhibitors.     

(Z)-2-(1H-1,2,4-三唑-1-基)-1-(2,3,4-三甲氧基苯)乙酮肟酯的合成和结构表征

合成了8个(Z)-2-(1H-1,2,4-三唑-1-基)-1-(2,3,4-三甲氧基苯)乙酮肟酯新化合物,经元素分析、IR、1H NMR、MS对其结构进行了表征。讨论了目标化合物的合成方法和立体化学结果。     

Target and non-target site mechanisms of fungicide resistance and their implications for the management of crop pathogens

Fungicides are indispensable for high-quality crops, but the rapid emergence and evolution of fungicide resistance have become the most important issues in modern agriculture. Hence, the sustainability and profitability of agricultural production have been challenged due to the limited number of fungicide chemical classes. Resistance to site-specific fungicides has principally been linked to target and non-target site mechanisms. These mechanisms change the structure or expression level, affecting fungicide efficacy and resulting in different and varying resistance levels. This review provides background information about fungicide resistance mechanisms and their implications for developing anti-resistance strategies in plant pathogens. Here, our purpose was to review changes at the target and non-target sites of quinone outside inhibitor (QoI) fungicides, methyl-benzimidazole carbamate (MBC) fungicides, demethylation inhibitor (DMI) fungicides, and succinate dehydrogenase inhibitor (SDHI) fungicides and to evaluate if they may also be associated with a fitness cost on crop pathogen populations. The current knowledge suggests that understanding fungicide resistance mechanisms can facilitate resistance monitoring and assist in developing anti-resistance strategies and new fungicide molecules to help solve this issue. © 2023 Society of Chemical Industry.     

Some Comments on a recently proposed method of determining chlormequat residues by derivatization with pentafluorothiophenol

A recent publication concerning the analysis of residues of the herbicide chlormequat in cotton seed by gas chromatography contains a significant error. A derivative prepared by reacting pentafluorothiophenol with chlormequat is actually produced by the reaction of the initial product of demethylation of chlormequat with a second molecule of pentafluorothiophenol. As the derivative is not derived from the chlormequat backbone, the method is not specific to chlormequat and could be misleading to an analyst using it or adapting it to other produce.     

Structure-activity relationships in a group of imidazole-1-carboxamides

Detailed structure-activity studies in a series of substituted imidazole-1-carboxamides culminated in the synthesis of N-alkyl-N-phenoxyalkyl substituted compounds and, eventually, prochloraz, a compound shown to give excellent broad-spectrum disease control in cereals. Subsequently, evidence was obtained which suggests that its mode of action is through the inhibition of ergosterol biosynthesis or, more specifically, through inhibition of sterol C-14 demethylation.     

Mutations in Cyp51 of Venturia inaequalis and their effects on DMI sensitivity

Journal of Plant Diseases and Protection - DMIs (sterol demethylation inhibitors) provide an important mode of action for control of Venturia inaequalis. They target the enzyme 14a-demethylase,...     

吡咯类农药活性化合物的研究进展

概述了具有农药活性的生物源吡咯类及相关结构的化合物,介绍了由吡咯类抗生素经化学结构改造而研究开发的溴虫腈等农药品种的发现过程、结构活性关系及应用研究概况,并对近10多年来合成吡咯类杀虫活性化合物的研究进展作了综述。     

Mosquito repellents: a review of chemical structure diversity and olfaction

Research on mosquito chemical repellents continues to advance, along with knowledge of mosquito olfaction and behavior, mosquito–host interactions and chemical structure. New tools and technologies have revealed information about insect olfactory mechanisms and processing, providing a more complex approach for the interpretation of how chemical repellents influence host‐seeking and feeding behavior. Even with these advances, there is still a large amount of information contained in the early works on insect repellents. Many of the standard test methods and chemicals that are still used for evaluating active repellents were developed in the 1940s. These studies contain valuable references to the activity of different structural classes of chemicals, and serve as a guide to optimization of select compounds for insect repellency effects. Copyright © 2010 Society of Chemical Industry     

Biochemical aspects of the fungitoxic and growth regulatory action of fenarimol and other pyrimidin-5-ylmethanols

The C-14 demethylation of the sterols, dependent on cytochrome P-450, and the C-22(23) desaturation of sterols are reactions in the ergosterol biosynthesis pathway that are regarded as primary target sites in the toxicity of fungicides of the pyrimidin-5-ylmethanol type. Currently, there is no evidence for target sites in other pathways of comparable sensitivity, although the failure of added ergosterol to reverse the fungitoxicity suggests the existence of such sites. The mitochondrial respiratory systems in Ustilago maydis and Aspergillus nidulans are insensitive to this type of fungicide and are not regarded as primary targets of fungitoxicity in these organisms. Appreciable evidence indicates that the primary targets in higher plant growth regulation are reactions, dependent on cytochrome P-450, that assist in the conversion of kaurene to kaurenoic acid in the gibberellin (GA) biosynthesis pathway. Growth retardation by high concentrations of pyrimidin-5-ylmethanols, which is not reversable by GA, apparently involves action at sites outside the GA biosynthesis pathway. The data derived from various studies of the mechanisms of fungitoxicity and growth regulation suggest that any undetected primary targets of the pyrimidin-5-ylmethanols are likely to be haem enzymes, similar to the cytochrome P-450 involved in sterol C-14 demethylation.