Structure—activity relationships for some organotin molluscicides

Bioassay data are reported for 12 organotin compounds, R₃SnX, against the adult snail, Biomphalaria glabrata, an intermediate host of schistosomiasis. The relationship between the molluscicidal activity and the nature of the R and X groups in the organotin compounds is discussed, as well as the possible mode of toxic action of these compounds.     

Structure—activity relationships of fungicidal acetylenic sulphones

Regression analysis in the l-alkylsulphonyl-2-arylacetylene series yielded significant correlations of antifungal activity against six microorganisms with certain physicochemical parameters (electronic effects, lipophilicity and steric factors). Fungicidal activity is enhanced by introducing electron-withdrawing substituents in the aryl nucleus, whereas variation of the lipophilic parameter reveals an optimum value. The results obtained indicate a mechanism of action based on a reaction of the compounds with nucleophiles present in the fungal cells, which was confirmed by determining the second-order rate constants of the reaction between 1 -alkylsulphonyl-2-arylacetylenes and the model nucleophile 4-nitro(thiophenol). The lipophilic para-meter was also determined experimentally using thin-layer chromatography. Regression analysis with this completely experimental set of parameters regression gave highly significant results in close agreement with those obtained above.     

Occurrences of Ceratocystis ulmi in Norway1

Norway (in contrast to Denmark and Sweden) has so far had only a few outbreaks of Dutch elm disease, all in the southern part of Norway (cities of Oslo and Drammen) on one or a few Ulmus glabra trees in city parks, not far from harbours and railways. Scolytus laevis endemic to Norway is the only potential vector found in the diseased trees. Transmission of the fungus through root grafts cannot be disregarded. The fungus is currently considered a dangerous foreign organism in Norway, subject to treatment according to the Norwegian phytosanitary regulations. Control measures, aiming at eradication, have been applied in all known cases of attack. Removal and destruction of diseased trees, stump treatment with herbicide, and covering of stumps with soil, have apparently been successful measures.     

Structure—activity relationships of pyridylcarbamates active against both benzimidazole-sensitive and -resistant isolates of Botrytis cinerea

A series of pyridylcarbamates showed high potency against cucumber gray mould (Botrytis cinerea Pers.). The most potent compound, propargyl-N-(6-ethyl-5-iodo-2-pyridyl)carbamate was effective against an isolate sensitive to benzimidazole and dicarboximide fungicides as well as against an isolate resistant to both types of compound. QSAR analyses and molecular modelling studies were carried out to investigate the structural requirements for highly active compounds and the structural feature of the binding site of each strain. Significantly different QSAR equations were obtained only for substituents at the 6-position of the pyridine ring. An ethyl-sized pocket or an ethyl terminal recognition was suggested in the case of the sensitive or resistant isolate respectively. These results could explain the phenomenon of negatively correlated cross-resistance between benzimidazoles and N-phenylcarbamate fungicides. Substituent effects at the 5- or 2-position were governed by steric factors. Substituent effects at the 3-position were explained by steric hindrance or by conformational effects. The propargyl-substituted compound above was the most desirable one from the viewpoint of QSAR.     

Structure—activity relationships in pyrethroid esters derived from substituted 2-phenoxy-3-methylbutanoic acids

Non-cyclopropane pyrethroid esters of different substituted 2-phenoxy-3-methylbutanoic acids have been synthesised using the three alcohols—3-phenoxybenzyl alcohol, α-cyano-3-phenoxybenzyl alcohol and 3, 4-methylene-dioxybenzyl alcohol. Among the 35 esters synthesised and tested against Culex quinquefasciatus Say, the Bancroftian filariasis vector, for both larvicidal and adulticidal activities, α-cyano-3-phenoxybenzyl 2-(4-fluorophenoxy)-3-methylbu-tanoate, with an LC₅₀ value of 2.5 × 10^?3 mg litre^?1 for larvicidal activity, and α-cyano-3-phenoxybenzyl-2-(4-chlorophenoxy)-3-methylbutanoate, with an LD₅₀ value of 30 times; 10^?4 ug insect^?1 for adulticidal activity, were found to be as effective as fenvalerate, a well-known non-cyclopropane pyrethroid ester. Structure-activity studies showed that the insecticidal activity is dependent on the nature and position of the substituent in the phenyl ring of the acid moiety and also on the type of alcohol moiety.     

The control in vitro of Ceratocystis ulmi by amine cations

Of 60 amine cations tested in vitro for activity against Ceratocystis ulmi, that of methyl benzimidazol-2-ylcarbamate (carbendazim) showed the highest activity, this being constant with three different associated anions. Some guanidines, 2-nitro-morpholine and 2-(thiazol-4-yl)benzimidazole (thiabendazole) showed considerable activity but a large group of alkylamines, 1-methylalkylamines and poly-amines were relatively inactive.     

Structure—activity relationship for some substituted dialkyl vinyl phosphates

The biological activity against the house fly, Musca domestica L., is reported for a series of dialkyl 2-bromo-1-(2,4-dichlorophenyl)vinyl phosphates. Maximum activity and the lowest degree of synergism with piperonyl butoxide were found with the dimethyl ester. Good activity was also shown by the diethyl ester. Both these compounds, used at the same dose, inhibited fly-head acetylcholinesterase. Compounds with longer alkyl chains were less effective and did not inhibit acetylcholinesterase.     

Formation of perithecia of Ceratocystis ulmi on natural and synthetic nutrient media

Ceratocystis ulmi formed fertile perithecia on 17 of 37 culture media tested, including many of the (autoclaved) natural substrates, but not on Saboraud's media or White's medium and not on potato dextrose agar (Table 1). Later, perithecia formed abundantly on four of eight variants of Zentmyer-Tchernoff agar medium (Table 2). This appears to be the first report on perithecia ofC. ulmi on an agar medium to which only synthetic nutrients were added. Both normal-strength and 110 diluted media gave perithecia. If only the sugar or only the asparagine-plus-salts were diluted, none or very few perithecia formed. Tenfold dilution of the vitamins did not affect results. Light did not prevent formation of perithecia.Samenvatting Ceratocystis ulmi vormde rijpe peritheciën op 17 van de 37 getoetste voedingsbodems, maar in het begin alleen op enkele van de (gesteriliseerde) natuurlijke voedingsbodems, niet op Sabourauds of Whites agar en evenmin op aardappel-dextrose-agar (Table 1). In latere proeven werden rijkelijk peritheciën gevormd op 4 van de 8 varianten op Zentmyer-Tchernoff-agar (Tabel 2).Waarschijnlijk is dit de eerste vermelding van vorming van peritheciën vanC. Ulmi op agar waaraan uitsluitend synthetische voedingsstoffen zijn toegevoegd. Zowel op de standaard-concentratie als op een tienvoudige verdunning van de voedingsstoffen werden peritheciën gevormd. Als alleen de glucose of alleen de asparagine-plus-zouten verdund waren, werden er geen of zeer weinig peritheciën gevormd. Tienvoudige verdunning van de vitaminen beïnvloedde de resultaten niet. Licht remde de vorming van peritheciën niet.A contribution of the Massachusetts Agricultural Experiment Station.     

Quantitative structure—activity relationships for nicotinanilide molluscicides

Structure-activity correlations for the toxicity of nicotinanilides to Biomphalaria glabrata have been studied in terms of partitioning, charge transfer and steric properties. Partition coefficients or πNA values (substituent constants for nicotinanilides, reflecting the influence on the partition coefficient of a substituent on the parent molecule) have been shown to contain a significant electronic component and to be related to chromatographically determined R_M values (derived from a relationship between the partition coefficient and R_F value for liquid-liquid chromatographic systems). There was no overall correlation between LC₅₀ values and partitioning, electronic or steric effects. However, for ten 4′-substituted nicotinanilides, the LC₅₀ values correlated significantly with partitioning, an increase in lipophilic character leading to an increase in biological activity. The greater activity of the unsubstituted parent compound could not be explained by purely advantageous steric effects but the 4′-position may be an important metabolic site. Use of compounds labelled with deuterium failed to clarify this point because no isotope effects were observed.     

Length and diameter of xylem vessels as factors in resistance of elms to Ceratocystis ulmi

Conductivity of the vascular system of 2-year-old shoots as regards air and water was higher in susceptible than in resistant elms. The xylem vessels of resistant elms were relatively shorter and the percentage of short vessels was greater than in susceptible elms. The percentage of vessels with a large diameter was smaller in resistant elms than in susceptible ones. These results might explain the limited spreading of the spores in the new annual ring of resistant elms.Samenvatting Tweejarige scheuten van resistente iepen bleken lucht en water minder snel door te laten dan vergelijkbare scheuten van vatbare iepen. De vaten bij resistente iepen waren relatief kort en het percentage korte vaten was groter dan bij vatbare iepen. Het percentage grote vaten was kleiner bij resistante iepen dan bij vatbare. Dit zou een verklaring kunnen zijn voor de relatief geringe verspreiding van de sporen in de nieuwe jaarring van de resistente iepen.     

Structure–activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae

BACKGROUND: Dengue fever is a severe public health problem for several countries. In order to find effective larvicides to aid control programs, the structure‐activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae were evaluated. Additionally, the composition and larvicidal activity of Syzygium aromaticum essential oil was assessed. RESULTS: Four compounds representing 99.05% of S. aromaticum essential oil have been identified. The essential oil was active against Ae. aegypti larvae (LC₅₀ = 62.3 and 77.0 ppm, field‐collected and Rockefeller larvae respectively). The larvicidal activity of eugenol, the major compound of the essential oil, was further evaluated (LC₅₀ = 93.3 and 71.9 ppm, field‐collected and Rockefeller larvae respectively). The larvicidal activity and structure‐activity relationships of synthetic derivatives of eugenol were also assessed. The larvicidal activity of the derivatives varied between 62.3 and 1614.9 ppm. Oxidation of eugenol allylic bond to a primary alcohol and removal of the phenolic proton resulted in decreased potency. However, oxidation of the same double bond in 1‐benzoate‐2‐methoxy‐4‐(2‐propen‐1‐yl)‐phenol resulted in increased potency. CONCLUSION: Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds. Copyright © 2012 Society of Chemical Industry     

Structure–degradability relationships for propyzamide analogues in soils

The kinetics of the degradation in soil of propyzamide and nine analogues have been measured at two temperatures (28 and 60°C). The degradation rates of propyzamide were determined in sterilised soil and in soil perfusates. The results obtained are in agreement with a chemical degradation of propyzamide and its analogues. Relationships were established between degradation rate constants and physicochemical parameters of the compounds: log k = ?aσ+bπ + c where σ = Hammett constant, π = hydrophobic constant, a, b, c are constants.     

The pyrethrins and related compounds. Part XLII:Structure–activity relationships in fluoro-olefin non-ester pyrethroids

A series of compounds containing fluorine atoms in place of hydrogen in olefinic non-ester pyrethroids has been synthesised using a route based on novel intermediates, ie 2-fluoroallyl acetates, which are coupled with aryl Grignard reagents, and tested against several insect species. In most cases, after introduction of fluorine at the olefinic position, the activity remains high in both the 1-aryl-1-(3-arylprop-2-enyl)cyclopropane and the (1-aryl-4-arylbut-2-enyl)cyclopropane series. In particular, the former series have potential as soil insecticides, because in tests against Diabrotica balteata, activities were high, and dose-transferability factors were increased by the introduction of fluorine. © 1999 Society of Chemical Industry     

1-alkylcyclopropanecarboxylates: An extension of pyrethroid structure—activity relationships

1-Alkylcyclopropanecarboxylic acids are synthesised by thermolysis of 1-pyrazolines prepared by 1,3-dipolarcycloadditions of diazoalkanes. The insecticidal and acaricidal activities of 14 pyrethroid esters of these acids are considered in relation to the influence of steric and metabolic factors on activity. 1-Alkyl compounds are less active than esters with no alkyl group at position 1, contrary to expectations, and also less active than the corresponding 2-alkyl esters.     

Organosilane insecticides. Part II: Chemistry and structure—activity relationships

Silicon effectively substitutes for quaternary carbon in etofenpr ox-type insecticides; the resulting dimethyl-4-ethoxyphenyl-3-(4-fluoro-3-phenoxyphenyl)propylsilane is a broad-spectrum insecticide with extremely low toxicity to fish. Four regions of this new silane insecticide have been systematically altered. The methyl groups on silicon appear to be critical for activity. Replacement of the fluorine with hydrogen results in a substantial loss of activity. The aromatic rings of the phenoxyphenyl fragment are best tethered by oxygen or carbonyl, the methylene and nitrogen analogs being of very low toxicity to the test species. The activity ranking of the methylene and carbonyl tethers is opposite to that found for ester pyrethroids. The relationship of insecticidal activity to the aromatic substituent para to the silicon atom has been found to correlate with the molar refractivity of the substituent. Replacement of a tetra-substituted carbon atom with a silicon atom can simplify construction of test compounds and thus be advantageously used in the exploration of structure—activity relationships. A novel method for preparing allylbenzenes from aromatic aldehydes was also developed.     

Allylamine antimycotics: Recent trends in structure—activity relationships and syntheses

Methods developed for the synthesis of terbinafine-related allylamine antimycotics are reviewed. The synthesis of the en-yne side chains were generally accomplished by means of organometallic reactions. The use of Pd⁰-catalysed coupling reactions allowed easy access to derivatives bearing sensitive side-chain substituents. As examples, four metabolites of terbinafine were prepared via this procedure. Investigations with the carbon analogue of terbinafine revealed that, within the allylamine antimycotics, the nitrogen appears to be necessary for penetration by the drug into the fungal cell. Replacement of the naphthalene moiety of terbinafine by optionally substituted benzo[b]thiophenes led to a number of derivatives with high antifungal activity. A series of benzo[b]thienyl compounds with the side chain at position 7 and different substituents at position 3 showed significantly increased activity against Candida albicans in vitro. In particular, the 3-chloro derivative with the allylamine side chain at position 7(SDZ 87–469) proved to be the most potent allylamine antimycotic reported to this date. Two novel types of lead structures, the homopropargylamines and the benzylamines show very high activity in vitro.     

Structure–biological activity relationships in triterpenic saponins: the relative activity of protobassic acid and its derivatives against plant pathogenic fungi

BACKGROUND: Triterpenic saponins from Sapindus mukorossi Gaertn. and Diploknema butyracea JF Gmelin were evaluated for in vitro antifungal activity against four phytopathogenic fungi. The study of the structure–antifungal activity relationships of protobassic acid saponins was widened by including semi‐synthetic derivatives. RESULTS: Diploknema butyracea saponins exhibited significant antifungal activity against three fungi (ED₅₀ 230–455 µg mL^?1), whereas S. mukorossi saponin was effective against two fungi (ED₅₀ 181–407 µg mL^?1). The n‐butanol extract after preparative HPLC separation provided two saponins from D. butyracea saponin mixture: 3‐O‐[β‐D ‐glucopyarnosyl‐β‐D ‐glucopyranosyl]‐16‐α‐hydroxyprotobassic acid‐28‐O‐[arabinopyranosyl‐glucopyranosyl‐xylopyranosyl]‐arabinopyranoside (MI‐I), and 3‐O‐β‐D ‐glucopyranosyl‐glucopyranosyl‐glucopyranosyl‐16‐α‐hydroxyprotobassic acid‐28‐O‐[arabinopyranosyl‐xylopyranosyl‐arabinopyranosyl]‐apiofuranoside (MI‐III). The single saponin extracted from S. mukorossi saponin mixture was identified as 3‐O‐[O‐acetyl‐β‐D ‐xylopyranosyl‐β‐D ‐arabinopyranosyl‐β‐D ‐rhamnopyranosyl] hederagenin‐28‐O[β‐D ‐glucopyranosyl‐β‐D ‐glucopyranosyl‐β‐D ‐rhamnopyranosyl] ester (SM‐I). Monodesmosides resulting from the partial degradation of hederagenin and hydroxyprotobassic acid bisdesmosides exhibited significant reduction in antifungal effect. Further removal of sugar moiety yielded complete loss in activity. The antifungal activity of the triterpenic saponins was associated with their aglycone moieties, and esterification of the hydroxyl group led to change in antifungal activity. CONCLUSION: Sapindus mukorossi saponin, which is effective against Rhizoctonia bataticola (Taub.) Briton Jones and Sclerotium rolfsii Sacc., can be exploited for the development of a natural fungicide. A sugar moiety is a prerequisite for the antifungal activity of triterpenic saponin. Copyright © 2010 Society of Chemical Industry     

Structure-activity relationships in triorganotin biocides: The influence of the anionic radical

Bioassay data are reported for seven triorganotin compounds (R₃SnX), in which R=phenyl, cyclohexyl, or 2-methyl-2-phenylpropyl, and × is the anionic form of the organic chelating ligands quinolin-8-ol, quinoline-8-thiol, 1,3-diphenylpropane-1,3-dione, or 3-hydroxyflavone, when tested against an organophosphorus-resistant species of the two-spotted spider mite (Tetranychus urticae), the potato blight fungus (Phytophthora infestans), and the vine downy mildew fungus (Plasmopara viticola). The relationship between the activity and the co-ordination number of the tin atom is discussed, and it is shown that the anionic group × can, in some instances significantly affect the biological properties.