The antifungal activity of some sulphonyl derivatives of isoxazole,pyrazole, thiazole and thiophene

Fifty-three heterocyclic sulphonyl derivatives including eight sulphonamides, three sulphonyl azides, nine sulphonohydrazides and twenty sulphonohydrazones of substituted thiophenes, and a smaller range of analogous isoxazoles pryazoles and thiazoles, were tested as potential fungicides in a simple screening procedure against Mucor mucedo, Septoria nodorum, Trichoderma viride, Chaetomium globosum and Aspergillus niger. Several thiophene-2-sulphonyl based compounds exhibited a high level of antifungal activity at 100 mg litre^?1 against the five test species, especially the mono-halogen-substituted sulphonamides and sulphonohydrazines, in which a single chlorine or bromine atom was substituted in the para position of an attached phenyl ring. The most active compound, against all five species of fungus was N-(4-chlorophenyl)-N-(trichloromethylthio) thiophene-2-sulphonamide which had average MIC₅₀ and MIC₁₀₀ values of 86 and 180 μmol respectively. (MIC₅₀ and MIC₁₀₀ values are, respectively, the concentrations required to inhibit fungal growth by 50% and to inhibit it totally.) In general, the isoxazole analogues of the thiophene-2-sulphonyl compounds exhibited a much lower fungitoxic activity, whilst the pyrazole and thiazole based compounds had little or no activity. Compared with the other results, the considerable activity shown by 4-[2′-(3,4-dichlorobenzylidene)hydrazinosulphonyl]thiophene-2-carboxylic acid was unexpected.     

Effects of organosilicon pyrethroid‐like insecticides on nerve preparations of American cockroaches and crayfish

Quaternary organosilicon pyrethroid‐like ethers (five compounds) and alkanes (three compounds) were used for neurophysiological tests. Their activities in inducing repetitive firing in the central nervous cord of the American cockroach (Periplaneta americana) were evaluated by an extra‐cellular recording method. The ethers were more active than the corresponding alkanes. The ability of the compounds to cause conduction blockage was also measured using the same nerve preparations, but the effects were too weak to allow definitive activity values to be determined. The compounds prolonged the sodium tail‐current in the crayfish giant axon under voltage clamp conditions. The rate of decay of the tail‐current changed in parallel with the reported insecticidal activity against P americana. These findings indicated that tail‐current activity was the most useful nerve parameter in predicting insecticidal activity. Regression analysis of the numerical data together with those reported for other alkanes revealed that the higher the tail‐current activity, the higher the insecticidal activity when a structural feature and the hydrophobicity were considered separately. The insecticidal activity of the ethers was about seven‐fold higher than that of the alkanes with equivalent tail‐current activity and hydrophobicity. Variations in insecticidal activity were parabolically correlated with the hydrophobicity [(log P)_opt = 9.1] when other factors were similar. © 2001 Society of Chemical Industry     

Inhibitors of juvenile hormone biosynthesis in corpora allata of the cockroach Periplaneta americana (L.) in vitro

The spontaneous biosynthesis of methyl (2E,6E)-(10R)-10,11-epoxy-3,7,11-trimethyldodeca-2,6-dienoate (juvenile hormone III; JH III) in excised corpora allata of Periplaneta americana was inhibited by a number of synthetic prop-2-ynyl ethers and 1,3-benzodioxole derivatives. One structurally diverse group of compounds inhibited only the final biosynthetic enzyme methyl farnesoate epoxidase (EC.1.14.14.–) at low to moderate concentrations, but at higher concentrations, also inhibited methyl farnesoate (MF) formation, causing an accumulation of MF in the concentration range 10 to 100 μM. For a second, more limited, group of compounds, there was close congruence between the inhibition of JH III biosynthesis and that of total ester (MF plus JH III) biosynthesis over their effective inhibitory concentration ranges. In contrast to the first group, there was no accumulation of MF and these compounds evidently inhibited JH III biosynthesis, at the level of either farnesoic acid esterification by O-methyl transferase (EC.2.1.1.–), or at an earlier step in the biosynthetic pathway that remains to be elucidated.     

New chlorinated juvenile hormone analogues and their biological activity

In the search for new juvenile hormone analogues (JHAs), a general approach was chosen based on the substitution of the isoprene unit, that carries the epoxy function in the natural hormone JHIII, by 3,3,3-trichloropropyl, 2,2-dichlorocyclopropyl- methyl, 3,3-dichloroallyl, or 3-chloroprop-2-ynyl groups. Accordingly, several terpenoid aromatic JHAs were prepared with, or without, oxygen atoms in the aliphatic chain. Structure-biological activity relationships of the most active compounds toward the yellow mealworm (Tenebrio molitor) and the large cabbage white butterfly (Pieris brassicae) are given. With a view to preparing synthetically accessible analogues, some alkyl phenyl ethers were also made, which were not branched in the aliphatic chain and were related terminally to the most active compounds. They were only moderately active against insects when tested for morphogenetic activity, but exhibited a good field persistence. The occurrence of a moderate acaricidal activity among these analogues prompted the examination of several 1,4-disubstituted-phenyl derivatives. The ovicidal effectiveness of these products against a susceptible strain of the two-spotted spider mite, Tetranychus urticae, was ten or 100 times higher than that of the well known and highly potent JHAs.     

Correlation between structure and phytotoxic activities of nitrodiphenyl ethers

Various nitrodiphenyl ethers were assayed using a cell-free photosynthetic system and intact microalgae to approach a correlation between chemical structure and their effect upon three biochemical processes: (1) linear photosynthetic electron transport (Hill reaction); (2) photophosphorylation (energy-transfer inhibition by affecting the ATP synthetase); and (3) light-induced peroxidative degradation of thylakoid lipids (formation of short-chain hydrocarbons). Diphenyl ethers with a p-nitro group at one phenyl ring and one or two chloro substituents at the other exhibit energy-transfer inhibition. Analogs with different substituents are ineffective. A moderate electron-transport inhibition is seen with almost all derivatives. The most obvious phytotoxic effect is the occurrence of light-induced peroxidation (of polyunsaturated fatty acids) by p-nitro- and p-nitrosodiphenyl ethers. Substituents such as -OCH₃, -OC₂H₅, -NHC₂H₅, or -COOCH₃, -CONHCH₃ next to the p-nitro group enhance peroxidative activity and are apparently important for stabilization and/or reactivity of a diphenyl ether radical originating through photosynthetic electron flow. Activity is further enhanced by substituents with positive Hammett parameters in ortho or para positions at the phenyl ring not carrying the nitro group.     

Miticidal pyrethroids having an isobutyranilidoxime ether skeleton

Isobutyranilidoxime meta-phenoxybenzyl ethers and related compounds were synthesized. Their insecticidal activities measured against Periplaneta americana by injection were lower than that of phenothrin by factors of at least 1/60. However, some compounds were comparable to or only slightly less potent than phenothrin and tetramethrin in miticidal activity tested by a contact method against Dermatophagoides farinae, D. pteronyssinus and Tyrophagus putrescentiae. © 1998 SCI     

Synthesis and precocious-metamorphosis-inducing activity of 3-pyridyl ethers

A new series of 5-(substituted phenoxy)pentyl 3-pyridyl ethers induced precocious metamorphosis in larvae of the silkworm, Bombyx mori. Both 2- and 4-pyridyl ethers were inactive, indicating that the 3-pyridine moiety was essential for the activity. Octyl, dodecyl and farnesyl 3-pyridyl ethers had no activity. Among the compounds tested so far, 5-(4-propylphenoxy)pentyl 3-pyridyl ether showed the highest activity. The activity fell off with increasing or decreasing length of the carbon chain between two oxygen atoms. Introduction of a methyl group at the 6 position of the pyridine ring completely eliminated the activity. Precocious metamorphosis induced by 3-pyridyl ethers was fully reversible by a simultaneous application of a small amount of tebufenozide, an ecdysteroid agonist, or methoprene, a JH agonist. © 1998 SCI.     

Pyridyl terpenoid ethers with high juvenile hormone activity

Pyridyl terpenoid ethers have outstanding juvenile hormone activity in Tenebrio molitor compared with their phenyl analogues (6,7-epoxy-3,7-dimethyloct-2-enyl 6-ethyl-3-pyridyl ether and 7-ethoxy-3,7-dimethyloct-2-enyl 6-ethyl-3-pyridyl ether are active at 100 pg/larva). The compounds were also active in Galteria mellonella and Culex pipiens.     

Synthesis and insecticidal properties of ether analogues of DDT-pyrethroids

Twenty-seven ethers which are structural analogues of DDT-pyrethroid insecticides have been synthesised. Bioassay data for these compounds against Lucilia cuprina, Blatella germanica and Heliothis punctigera are presented and the structure-activity relationships (SAR) discussed. The SAR of the new series of ether analogues are compared and contrasted to those of their parent DDT-pyrethroid compounds.     

Pyrethroid insecticides derived from 2,2-dimethyl-3-(3-phenoxybenzyloxy)propanal

Fourteen oxime ethers and eleven other unsaturated compounds derived from 2,2-dimethyl-3-(3-phenoxybenzyloxy)propanal were synthesised and their insecticidal activity against Musca domestica, Locusta migratoria, Dysdercus cingulatus, Aedes aegypti, Plutella xylostella, Drosophila melanogaster, Tetranychus urticae and Spodoptera littoralis tested. Structural variations including chain length, branching and unsaturation of the oxime ether O-alkyl group and substituent exchange at the carbon-carbon double bond of the unsaturated compounds were made in order to examine the structure-activity relationship. All biological activities were compared with the activity of the ether pyrethroid MTI-500.     

Structure-activity relationships in a series of new antifungal nitroalcohol derivatives

The structure-antifungal activity correlations of 23 new nitroalcohol derivatives (1-substituted-2-nitropropane-1, 3-diols, their ethers and esters) were investigated using a generalised quantitative structure-activity relationships (QSAR) method, combining Golender and Rozenblit's logico-structural approach and the Free-Wilson and Hansch analyses. Based on results obtained from principal component analysis, the in-vitro activities against Helminthosporium sativum, the inhibition of germination and of growth could be assumed to be governed by a common mechanism. It is suggested that the antifungal activity of the compounds studied is determined mainly by the presence or absence of an aromatic ring (unsubstituted, or bearing a hydrophobic group that is small in bulk and electron-attracting) at position 1, of a (potential) double bond between carbon atoms 1 and 2, and of an acyloxy group at position 3. Among these factors, the double bond seems to be the most important, and the mechanism of the antifungal action is probably dependent on the reactivity of this bond towards thiol groups of endogenous substances.     

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.     

Quantitative structure-activity relationships of the inhibition of photosynthetic electron flow by substituted diphenyl ethers

The effect of 41 substituted diphenyl ethers (derivatives of nitrofen and chloroxuron) on photosynthesis in isolated spinach chloroplasts has been studied. All the chemicals were found to be inhibitors of non-cyclic electron transport; the pI₅₀ values varied from 3.17 to 7.16 (I₅₀ is the molar concentration causing 50% inhibition; pI₅₀= -log I₅₀). Based on their structures, the compounds were divided into four groups; for most groups, a correlation between the inhibition of photosynthesis and physicochemical parameters was found. Lipophilicity proved to be the most important parameter; electronic effects did not play a role. Introduction of substituents into the nitrophenyl ring of nitrofen lowered activity considerably. Nitrofen and and chloroxuron analogues seemed to inhibit at different sites in the electron transport chain. A relationship between inhibition of photosynthesis and herbicidal activity was not clear.     

Synthesis of substituted benzyl 2-methyl-2-phenylpropyl ethers and their moth-proofing activity on wool against larvae of Anthrenus fasciatus

Synthesis of new moth-proofing agents is necessary to overcome the damage caused by clothes moths and carpet beetles to hosiery and upholstery. In the present paper substituted benzyl 2-methyl-2-phenylpropyl ethers were synthesised and evaluated for moth-proofing activity. Two compounds were found to provide protection against larvae of Anthrenus fasciatus at levels of 1.0 and 10 g kg⁻¹ respectively. The introduction of a methyl group in the para position of the benzene ring attached to C₂ of the 2-methylpropyl chain (ring A) increased moth-proofing activity. The introduction of a phenoxy ring at the meta position of the benzyl nucleus (ring B) also increased activity, while the presence of a nitro group on the benzyl nucleus (ring B) decreased activity. © 1999 Society of Chemical Industry     

Synthesis and bioactivity evaluation of novel spiromesifen derivatives

BACKGROUND: The development of environmentally friendly and novel structural pesticides is now an area of intense research in the agriculture field. Spirocyclic tetronic acids such as spiromesifen are typical compounds of this kind. In order to discover novel compounds with improved and broader-spectrum insecticidal activities, a series of spiromesifen derivatives were synthesised and bioassayed. RESULTS: The derivatives were identified by ¹H NMR and MS. Preliminary bioassays demonstrated that some bioactivities of compounds 5a to 5u were better and had a broader spectrum than the lead compound spiromesifen. Moreover, these compounds showed better insecticidal activities against Mythimna sepatara and Aphis fabae than acaricidal activities against Tetranychus cinnabari. Furthermore, LC₅₀ of 5s against Aphis fabae reached 1.09 mg L⁻¹. At the same time, compounds 5g, 5i, 5k and 5r also warrant further study because of their superior bioactivities to spiromesifen. What is more, suitable carbon chain length in the 4-position ester and the log P value of these spiromesifen derivatives dramatically influenced their insecticidal activities. Butyric or pentanoic ester and a log P value of 4.0–6.0 may be preferred. CONCLUSION: The present work demonstrates that some spiromesifen derivatives can be used as potential lead compounds for developing novel insecticides and acaricides. Copyright © 2011 Society of Chemical Industry     

Studies on pathogenesis of Rhizoctonia solani in beans: an evaluation of the possible roles of phenylacetic acid and its hydroxy derivatives as phytotoxins

All isolates of Rhizoctonia solani used in this study, when grown in Weinhold medium supplemented with phenylalanine, accumulated phenylacetic acid (PAA) and its ortho-, meta- and para-hydroxy derivatives in culture. Major metabolites which accumulated were PAA and m-hydroxyphenylacetic acid (m-OH-PAA). However, the accumulation in vitro of total phenylacetic acid derivatives by isolates of R. solani was not related to their pathogenicity and/or virulence. On the contrary, the non-pathogenic and weakly virulent isolates of R. solani produced the highest quantities of PAA-derivatives per unit weight of mycelium in comparison to the highly virulent isolates.The phenylacetic acid derivatives used in this investigation, when bioassayed at high concentrations, caused inhibition of growth of tomato and bean seedlings. The most active compounds were PAA and -α-methoxy-phenylacetic acid (MeO-PAA). However, when m-OH-PAA was assayed at low concentrations there was a stimulation of seedling growth. In addition, when m-OH-PAA solutions were injected into bean hypocotyls or into tobacco leaves they never caused necrotic lesions or symptoms resembling those caused by R. solani on beans.These results indicate that PAA-derivatives are not directly involved in pathogenesis of R. solani in beans.     

Insecticidal properties of monoterpenoid derivatives to the house fly (diptera: Muscidae) and red flour beetle (coleoptera: Tenebrionidae)

Monoterpenoid derivatives were synthesized and their insecticidal activities were evaluated against red flour beetles, Tribolium castaneum (Herbst), in fumigant bioassays and against house flies Musca domestica (L.) in topical, fumigant, and ovicidal bioassays. Acetate derivatives and haloacetate derivatives were compared with each other, and with the parent monoterpenoid to determine structure-activity relationships. Acetate derivatives were more active than the propionate derivatives of cyclic monoterpenoids in the topical, fumigant, and ovicidal bioassays. Pivalates were topically more insecticidal than acetates to adult house flies, while the acetates had the greater ovicidal activity. Acetates and pivalates were more effective than haloacetates in the topical, red flour beetle fumigation and ovicidal bioassays. Fluoroacetates of cyclic monoterpenoids were the most effective house fly fumigants, followed by acetates, and trichloroacetates. Several derivatives were produced that displayed enhanced activity relative to the parent alcohols or phenols.     

姜黄素异噁唑和吡唑衍生物的合成及杀螨活性

为了寻求和开发新的基于天然产物的杀螨剂,在明确姜黄素具有杀螨活性,且其结构中的双羰基并非杀螨活性关键基团的基础上,设计并合成了15个姜黄素异噁唑和吡唑衍生物,其结构均经红外光谱、核磁共振氢谱和质谱分析确认。生物活性测定结果表明:几乎所有的目标化合物对朱砂叶螨Tetranychus cinnabarinus和柑橘全爪螨Panonychus citri均表现出了比先导化合物姜黄素更优异的触杀活性,其中化合物 4和11 的活性最为突出。处理48 h后,化合物 4 对朱砂叶螨和柑橘全爪螨的LC50值分别为333.0和156.0 mg/L,其毒力是姜黄素的6.35和4.56倍, 11 的LC50值分别为478.4和144.7 mg/L,毒力是姜黄素的4.42和4.92倍;相应地处理72 h后, 4 的LC50值分别为115.0和84.9 mg/L,其毒力是姜黄素的5.02和1.43倍, 11 的LC50值分别为91.0和68.7 mg/L,毒力是姜黄素的6.35和1.77倍。化合物 4和11 可作为进一步开发研究的具有杀螨活性的候选化合物。     

Plant growth regulating properties of 1-amino-1-methylethylphosphonic acid and its derivatives

Seventeen derivatives of 1-amino-1-methylethylphosphonic acid were synthesised and evaluated for plant-growth-regulating activity using Cucumis sativus and Triticum aestivum. The tested compounds exerted either moderate herbicidal action or stimulated plant growth. The structure-activity relationships were similar to those observed earlier for the derivatives of 9-aminofluoren-9-ylphosphonic acids (phosphonic analogues of morphactins).     

基于植物代谢组学和昆虫肠道细菌分析光肩星天牛的寄主适应性

为探究光肩星天牛Anoplophora glabripennis对传统抗性树种白蜡的适应性机制,利用代谢组学分析不同白蜡品种木质部次生代谢产物,利用16S rRNA测序技术对取食白蜡后的光肩星天牛肠道细菌群落组成进行检测,并采用Pearson方法分析两者的相关性。结果表明,在洋白蜡Fraxinuspennsylvanica和中国白蜡F. chinensis木质部中共筛选出27类抗虫性差异代谢产物,其中黄酮苷、双黄酮及多黄酮、简单酚类、香豆素及其衍生物和木质素苷在中国白蜡中含量较丰富;而2-芳基苯并呋喃类黄酮、阿朴啡类、麦角林及其衍生物和有机氮化合物在洋白蜡中占优。光肩星天牛取食洋白蜡和中国白蜡2种寄主后肠道细菌群落组成存在明显差异,优势菌门分别为变形菌门和厚壁菌门;优势菌属分别为拉乌尔菌属Raoultella（55.79%）和乳球菌属Lactococcus（57.52%）;筛选到21个差异菌属,其中13个菌属在中国白蜡中的相对丰度显著高于洋白蜡。相关性分析结果表明,尽管类黄酮、简单酚类、香豆素及其衍生物和木质素苷等酚类化合物在中国白蜡中含量更高,但取食中国白蜡后光肩星天牛肠道内一方面存在优势菌群参与代谢上述物质,如肠球菌属Enterococcus、拉乌尔菌属对类黄酮和木质素苷的代谢;另一方面中国白蜡通过一些特异菌属和共有菌属的增殖参与代谢,如乳杆菌属Lacto-bacillus和放线菌属Actinomycetes对类黄酮、乳球菌属对简单酚类、鞘氨醇杆菌属 Sphingobacterium对香豆素及其衍生物、放线菌属和肠球菌属对木质素苷的代谢。生物碱在中国白蜡中的含量低于洋白蜡,未发现特殊菌属降解该类物质。推测相对于洋白蜡,取食中国白蜡后光肩星天牛肠道菌群更具特异性和多样化,可以帮助光肩星天牛快速代谢相关次生物质,顺利完成其在中国白蜡上的生活史。