Inhibitory effect of bacterial ubiquinones on the settling of barnacle,Balanus amphitrite

In an attempt to clarify the influence of marine bacteria on the settling of fouling invertebrate larvae, we screened for inhibitors, produced by marine bacteria, of settling by cyprids of the barnacle,Balamus amphitrite. We found that the culture broth ofAlteromonas sp. strain number KK10304, which was associated with the marine sponge,Halichondria okadai, effectively inhibited settling of the cyprids. Bioassay-guided isolation indicated ubiquinone-8 (1) as an effective inhibitor of cyprid settling. As ubiquinones are widely distributed in bacteria, several related compounds were also tested.     

Biological activity of flucycloxuron,a novel benzoylphenylurea derivative,onTenebrio molitor: comparison with diflubenzuron and triflumuron

Flucycloxuron, a novel benzoylphenylurea (BPU) derivative, exhibited insecticidal activity when injected into newly ecdysed pupae ofTenebrio molitor. Mortality occurs because of defective adult ecdysis. Treatment caused a reduction in both cuticle thickness and incorporation of¹⁴C-labelled precursor into chitin, although it had no significant effect on the protein synthesis. The potencies of other BPU compounds as inhibitors of chitin biosynthesis have been examined and results showed that diflubenzuron was less effective than either flucycloxuron or triflumuron.     

Activité tuberculostatique de thiouréesortho- etméta-substituées

Summary A large number of substituted thioureas and related compounds, the molecular structure of which diverges more or less from that of the classical 4-4-disubstituted thiocarbanilides, have been tested forin-vitro tuberculostatic activity; many of them have proved effective at a concentration of 10^–5.     

Activité tuberculostatique de nouvelles N,N′-diarylthiourées

Summary A number of new diversely substituted thiocarbanilides and N-aryl-N-naphthylthioureas have been found which display pronounced tuberculostatic activityin vitro. One of these compounds, 4-ethyl-4-isoamyloxythiocarbanilide, proved to be particularly effective.     

Green leaf volatiles interrupt aggregation pheromone response in bark beetles infesting southern pines

Summary Green leaf volatiles were shown to interrupt responses to aggregation pheromones of three species of bark beetles (Coleoptera: Scolytidae) which infest pines in the southern United States [the southern pine beetle,Dendroctonus frontalis Zimm.; the four-spined engraver,Ips avulsus (Eichhoff); and the five-spined engraver,Ips grandicollis (Eichhoff)]. The order of effectiveness of the compounds tested for each species was hexanal>hexanal+hexan-1-ol>hexan-1-ol. Neither hexanal, hexan-1-ol nor hexanal+hexan-1-ol was as effective in interrupting pheromone responses ofD. frontalis as verbenone, a known inhibitor of this species. Other than interspecific chemical signals, this is the first report of an interruptant forIps species, and the only report of a pheromone interruptant active for bothIps andDendroctonus species.     

Comparison of the effects of imidazo[1,2-a]pyridine-2-carbamates and benzimidazole-2-carbamates on the development ofHymenolepis nana inTribolium confusum

Summary The anthelmintic properties of several imidazo[1,2-a]pyridine carbamates and benzimidazole carbamates againstHymenolepis nana are compared. The results of this study, coupled with previous work, indicate that methyl 6-(trichloroethenyl)-imidazo[1,2-a]pyridine-2-carbamate has the potential of being a broad spectrum anthelmintic, effective against both nematodes and cestodes.Acknowledgments. We are indebted to Miss Marianne Hardy for excellent technical assistance. Our sincere thanks are extended to the Merck, Sharp & Dohme and Hoechst companies for the compounds tested in the present study.     

Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase 3

Alcohol dehydrogenase 3 (ADH3) has been assigned a role in nitric oxide homeostasis due to its function as an S-nitrosoglutathione reductase. As altered S-nitrosoglutathione levels are often associated with disease, compounds that modulate ADH3 activity might be of therapeutic interest. We performed a virtual screening with molecular dockings of more than 40,000 compounds into the active site of human ADH3. A novel knowledge-based scoring method was used to rank compounds, and several compounds that were not known to interact with ADH3 were tested in vitro. Two of these showed substrate activity (9-decen-1-ol and dodecyltetraglycol), where calculated binding scoring energies correlated well with the logarithm of the k _cat/K _m values for the substrates. Two compounds showed inhibition capacity (deoxycholic acid and doxorubicin), and with these data three different lines for specific inhibitors for ADH3 are suggested: fatty acids, glutathione analogs, and cholic acids.     

Discovery of novel avermectins with unprecedented insecticidal activity

Summary A new class of insecticidal and antiparasitic agents, 4-amino-4-deoxy avermectins, has been developed by chemical modification of avermectin B₁. The most effective of these compounds are 1500-fold more potent than avermectin B₁ (abamectin) against the beet armywormSpodoptera exigua and show similar potency against other lepidopteran larvae.     

Activité staphylostatique de composés du groupe des benzophénarsazines

Summary It is shown that certain compounds belonging to the group of angular benzophenarsazines display a high specific bacteriostatic activity towardsMicrococcus pyogenes var.aureus. This biological property provides a further ground of similarity between these compounds and one of their structural analogues, 3,4–5,6-dibenzocarbazole.     

Arylpyridyl-thiosemicarbazones: A new class of anti-juvenile hormones active against Lepidoptera

Summary A new class of anti-juvenile hormone agents is described. Active anti-juvenile hormone compounds were either diazine thiosemicarbazones or aryl substituted pyridyl thiosemicarbazones, synthesized from substituted benzaldehydes. While many analogs in these classes showed feeding and growth inhibition in a variety of insects, a select group caused formation of precocious pupal characteristics inAgrotis ipsilon (black cutworm) andHeliothis virescens (tobacco budworm) and black cuticle and precocious pupae inManduca sexta (tobacco hornworm). They were active only by diet incorporation. The symptoms of precocious development could be reversed by co-administration of a juvenoid. One of the active compounds was shown to inhibit juvenile hormone biosynthesis in vitro by corpora allata of the cockroachDiploptera punctata. However, none of the compounds were active inhibitors of purified chicken liver prenyl transferase.     

Animalisation de l'œuf de l'oursinParacentrotus lividus par des substances polysulfoniques

Summary The effects of two compounds with sulfonic acid groups, chlorazol sky blue and Germanin (Bayer 205), are being studied on the developing egg of the sea urchin,Paracentrotus lividus. The chlorazol sky blue (1/5000) is a very effective animalizing agent. In dilute solutions (1/25000 and 1/100000), it induces the development of radial larvae. The lithium chloride counteracts the animalizing effects of chlorazol sky blue. The Germanin has an animalizing effect only at high concentrations. The penetration of these agents appears essential for the animalization. The reaction of the sulfonic acid groups with the basic groups of the intracellular proteins appears to be concerned with the animalizing effect. The results of these experiments are discussed in relation to the animalizing effects of various sulfonated dyes and zinc ions.     

Enzymatic formation of potential anticancer and antiviral inosine analogues

Theoretically, inosine analogues should act as effective inhibitors of tumor cell proliferation and viral replication. To acquire a broad spectrum of new candidate inosine analogues, a rapid, facile, quantitative and stereoselective method for deaminating potential antitumor and antiviral adenine analogues previously synthesized in our laboratory was developed. A novel 5-adenylic acid deaminase, with relaxed substrate requirements, fromAspergillus species was utilized to deaminate four hexofuranosyladenine nucleosides and five adenine nucleoside dialdehydes to their corresponding inosine analogues. The fastest rates of deamination for the hexofuranosyl nucleosides were for the compounds where the vicinal hydroxyl groups on the sugars are oriented in the erythro configuration. For rapid deamination of the adenine nucleoside dialdehydes, theR configuration at the proximal carbon atom is preferred, while the nature of the group on the distal carbon atom has no significant effect on the rate or extent of deamination.     

A simple method for in vivo testing of glandular enzymatic activity on potential precursors of larval defensive compounds inPhratora species (Coleoptera: Chrysomelinae)

The presence of glandular -glucosidase and oxidase-specific activities, and the possible role of phenolglucosides and related compounds as precursors for larval defensive compounds, were directly demonstrated by introducing salicin, saligenin and helicin into the defensive glands ofPhratora species.Ph. tibialis andPh. laticollis that normally secrete endogenously-produced iridoid monoterpenes and do not use phenolglucosides from their food sources as precursors, were able to produce salicyladehyde from helicin when the latter was introduced into the defensive glands.     

The male pheromone of the old house borerHylotrupes bajulus (L.) (Coleoptera: Cerambycidae): Identification and female response

We report here the identification of the long-range, male-produced sex pheromone of the Old house borerHylotrupes bajulus. Chemical analysis of hexane extracts obtained by surface extraction from dissected prothoracic glands and from headspace samples of the two sexes, revealed male-specific compounds: (3R)-3-hydroxy-2-hexanone, 2-hydroxy-3-hexanone, the diastereomeric diols (2R, 3R)-2,3-hexanediol and (2S, 3R)-2,3-hexanediol, 2,3-hexanedione, as well as 1-butanol.In wind tunnel bioassays we tested the influence of these male-specific compounds from the prothoracal glands on the behaviour of unmated and mated females. Specific behavioural sequences of the tested females (activity, running behaviour, searching, cleaning, flying, extension of ovipositor) were recorded. Unmated females were attracted by male beetles, headspace extracts of males, synthetic blends of the major pheromone compounds as well as by the components (3R)-3-hydroxy-2-hexanone, and the diastereomeric diols. Hexane, female beetles and 2,3-hexanedione did not attract unmated females. The reactions of mated females to male beetles and headspace samples did not differ significantly from those of the controls.The results of the bioassays show that the two-stage premating behaviour is initiated by emission of a long-range sex pheromone from the male prothoracal glands, which functions as an activator, attractant, and possibly aphrodisiac for unmated females.     

Dérivés trifluorométhylés des [1]benzothiopyrano[4,3-b]indoles et des 6H-[1]benzothiopyrano-[4,3-b]quinoléines

Summary Some fluoro derivatives of [1]benzothiopyrano[4,3-b]indoles and 6H[1]benzothiopyrano[4,3-b] quinolines have shown carciuogenic activities in regard to the fluorine position; we thought it interesting to prepare some trifluoromethyl analogs of there compounds to study the biological activities and to compare with other compounds of the same family. In the present work, we report the synthesis of 7-trifluoromethyl and 8-trifluoromethyl [1]thiochroman-4-one and some [1]benzothiopyrano[4,3-b]indoles and quinolines substitued in 3 or 4 position which have been obtained from these two ketones.     

Dynamics of excretion of urinary chemosignals in the house mouse (Mus musclus) during the natural estrous cycle

Summary The volatile fraction of urinary metabolites was investigated chromatographically at five different stages of the natural estrous cycle. A very substantial endocrine dependency has been noted for 11 compounds: 4 ketones, 2 acetate esters, 3 dihydrofuran isomers, dehydro-exo-brevicomin, and 2,5-dimethylpyrazine. The compounds were structurally verified through combined gas chromatography/mass spectrometry.     

Accumulation of phenylpropanoids in the rectal glands of males of the Oriental fruit fly,Dacus dorsalis

Summary Two phenylpropanoid compounds, 2-allyl-4,5-dimethoxyphenol(II) and coniferyl alcohol(III), were characterized from body tissue of wild males of the Oriental fruit fly,Dacus dorsalis. These compounds accumulated in the rectal glands only when laboratory-reared males were fed with methyl eugenol. Compound II was released into the air during dusk, which coincides with the fly courtship period. Pheromonal and allomonal effects of the phenylpropanoids were examined.     

Zur Frage des Vorkommens von N-Nitroso-Verbindungen im Tabakrauch

Summary Important facts in connection with the occurrence of N-Nitroso compounds in tobacco smoke have been summarized. This paper reports on analytical methods for the identification of N-Nitroso compounds. The figures known about nitrate content and volatile bases of tobacco, as well as the nitrogen oxides and volatile bases of tobacco smoke as precursors of N-Nitroso compounds, are summarized. The third order reaction of secondary amines with an equimolar mixture of nitric oxide and nitrogen dioxide is a precondition for the formation of N-Nitroso compounds in tobacco smoke. While examining tobacco smoke for N-Nitroso compounds, temperature and time conditions have to be adapted to the natural smoking process. The use of solvent as well as cold traps has to be avoided to exclude the formation of artifacts. Analyses completed under these conditions furnished results of 0.004µg of a mixture consisting of N-Nitroso-dimethylamine and N-Nitroso-pyrrolidine, calculated as N-NO per cigarette. A number of animalexperimental preconditions are still lacking, to judge the biological effects of these extraordinarily small amounts of N-Nitroso compounds.     

Constituents of Egyptian Euphorbiaceae. IX. Irritant and cytotoxic ingenane esters fromEuphorbia paralias L.

Summary The irritant and cytotoxic constituents of the latex ofEuphorbia paralias L. were separated from the hydrocarbon fraction by means of solvent partition. 3 new ingenane esters were identified from the toxic ether fraction. The major compound was 3-angelyl-20-deoxyingenol and the 2 minor compounds were 3-hexanoyl-20-deoxyingenol and 3-angelylingenol. These compounds were of a similar potency to podophyllin in the inhibition of³H-thymidine uptake by TLX/5 mouse lymphoma cells. In addition the compounds produced a persistent erythema of the mouse ear in sub-microgram doses.Acknowledgments. F.J. Evans is grateful to the Royal Society for a travel grant.     

<Emphasis Type="Italic">Anopheles gambiae</Emphasis> odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents

Insect odorant binding proteins (OBPs) are the first components of the olfactory system to encounter and bind attractant and repellent odors emanating from various sources for presentation to olfactory receptors, which trigger relevant signal transduction cascades culminating in specific physiological and behavioral responses. For disease vectors, particularly hematophagous mosquitoes, repellents represent important defenses against parasitic diseases because they effect a reduction in the rate of contact between the vectors and humans. OBPs are targets for structure-based rational approaches for the discovery of new repellent or other olfaction inhibitory compounds with desirable features. Thus, a study was conducted to characterize the high resolution crystal structure of an OBP of Anopheles gambiae, the African malaria mosquito vector, in complex with N,N-diethyl-m-toluamide (DEET), one of the most effective repellents that has been in worldwide use for six decades. We found that DEET binds at the edge of a long hydrophobic tunnel by exploiting numerous non-polar interactions and one hydrogen bond, which is perceived to be critical for DEET’s recognition. Based on the experimentally determined affinity of AgamOBP1 for DEET (K _d of 31.3 μΜ) and our structural data, we modeled the interactions for this protein with 29 promising leads reported in the literature to have significant repellent activities, and carried out fluorescence binding studies with four highly ranked ligands. Our experimental results confirmed the modeling predictions indicating that structure-based modeling could facilitate the design of novel repellents with enhanced binding affinity and selectivity.