Sand Fly larvae are capable of positive chemotaxis: a proof of concept study using Phlebotomus papatasi (Diptera: Psychodidae) as a model species.

Phlebotomine sand flies are important vectors of medical and veterinary importance, transmitting pathogens, such as the Leishmania parasites, responsible for 700,000 to 1 million new cases of leishmaniasis every year. The vast majority of the current sand fly surveillance and control tools are tailored against the adult stages, due to the limited knowledge on the ecology of the larval stages. Since vector control is primarily an ecological problem, an in-depth understanding of the behavior of the target insect pests across all the different life stages of their development is required prior to the development of effective control strategies. It is well known that chemical cues play an important role in insect behavior. While there are numerous studies investigating the behavior of adult sand flies in response to chemical sources, there is currently no information available on the response of their larval stages. In this study, novel bioassays were constructed to investigate the effect of chemical cues (gustatory and olfactory) on the behavior of Phlebotomus papatasi (Scopoli) sand fly larvae. The larvae exhibited a clear food preference within a few hours of exposure in a 2-choice bioassay, while, also, demonstrated positive chemotaxis in response to volatile stimuli emitted from their preferred food source. Identification of the specific chemical compounds (or the combination thereof) eliciting attractance response to sand fly immature stages could lead to the development of innovative, and targeted (larval-specific) tools for the surveillance, and management of these important public health pests.

Studies on the Volatiles Composition of Stored Sheep Wool, and Attractancy toward Aedes aegypti Mosquitoes.

To discover new natural materials for insect management, commercially available stored sheep wool was investigated for attractancy to female adult Aedes aegypti mosquitoes. The volatiles from sheep wool were collected by various techniques of headspace (HS) extractions and hydrodistillation. These extracts were analyzed using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detector (GC-FID) coupled with GC-MS. Fifty-two volatile compounds were detected, many of them known for their mosquito attractant activity. Seven compounds were not previously reported in sheep products. The volatile composition of the extracts varied significantly across collections, depending on the extraction techniques or types of fibers applied. Two types of bioassay were conducted to study attractancy of the sheep wool volatiles to mosquitoes: laboratory bioassays using glass tubes, and semi-field bioassays using large, screened outdoor cages. In bioassays with glass tubes, the sheep wool hydrodistillate and its main component, thialdine, did not show any significant attractant activity against female adult Ae. aegypti mosquitoes. Semi-field bioassays in two large screened outdoor cages, each equipped with a U.S. Centers for Disease Control (CDC) trap and the various bait setups with Vortex apparatus, revealed that vibrating wool improved mosquito catches compared to the setups without wool or with wool but not vibrating. Sheep wool, when vibrated, may release intensively volatile compounds, which could serve as olfactory cues, and play significant role in making the bait attractive to mosquitoes. Sheep wool is a readily available, affordable, and environment-friendly material. It should have the potential to be used as a mosquito management and surveillance component in dynamic bait setups.

Structure-Activity Relationship Analysis of Potential New Vapor-Active Insect Repellents.

A total of 115 aryl amides were synthesized and screened for vapor repellency against the Orlando (OR) strain of Aedes aegypti mosquitoes. Of these compounds, 29 had 1 h repellency EC50 values comparable to or better than N,N-diethyl-meta-toluamide (DEET, 1 h EC50 value of 35 µg/cm2), with 2,2,3,3,3-pentafluoro-N-(4-fluorophenyl)propenamide (53) and 2,2,3,3,4,4,4-heptafluoro-N-(3,4,5-trifluorophenyl)butanamide (101) exhibiting the most potent EC50 values of 4.5 and 2.9 µg/cm2, respectively. The cross-resistance of select, highly potent, derivatives against the pyrethroid-resistant Puerto Rico (PR) strain of A. aegypti was also investigated, and little to no resistance was observed. When synergized with 1R-trans-permethrinic acid (TFA), compound 101 had a 1 h EC50 value 6 times lower than metofluthrin against OR and 40 times lower against PR mosquitoes. Additionally, preliminary mammalian oral toxicity was screened for compounds 69 and 101, and both exhibited LD50 values of >2000 mg/kg. The structure-activity relationship analysis, which guided the synthesis of these derivatives, is given, and key trends are highlighted to inform future analogue design.

Interactions of DEET and Novel Repellents With Mosquito Odorant Receptors.

The carboxamide N,N-di-ethyl-meta-toluamide (DEET) is the most effective and widely used insect repellent today. However, drawbacks concerning the efficacy and the safety of the repellent have led to efforts to design new classes of insect repellents. Through quantitative structure-activity relationships, chemists have discovered two chemical groups of novel repellents: the acylpiperidines and the carboxamides, with the acylpiperidines generally more potent in biological assays. Although the exact mechanism of action of DEET and other repellents has not yet been thoroughly elucidated, previous research shows that the activity of insect odorant receptors are inhibited in the presence of repellents. The present electrophysiological study employs two-electrode voltage clamp with Xenopus laevis oocytes expressing AgOR2/AgOrco and AgOR8/AgOrco receptors to assess the effects of the novel repellents on Anopheles gambiae Giles (Insecta: Diptera: Culicidae) mosquito odorant receptors. The novel acylpiperidines and carboxamides reversibly inhibited (12-91%) odorant-evoked currents from both AgOR2/AgOrco and AgOR8/AgOrco receptors in a dose-dependent manner at all tested concentrations (30 µM to 1 mM). Furthermore, all the novel agents were more potent inhibitors of the receptors than DEET, with the acylpiperidines producing on average greater inhibition than the carboxamides. Interestingly, there was a correlation (r2 = 0.72) between the percentage inhibition of AgOR2/AgOrco receptor currents and protection times of the acylpiperidines. Our results add to existing evidence that the repellency of a compound is linked to its ability to disrupt the insect olfactory system and that the acylpiperidines could represent a class of more effective alternatives to the current gold standard, DEET.

Screening for Enhancement of Permethrin Toxicity by Plant Essential Oils Against Adult Females of the Yellow Fever Mosquito (Diptera: Culicidae).

Aedes aegypti L. (Diptera: Culicidae) is one of the most medically important mosquito species, due to its ability to spread viruses of yellow fever, dengue fever, and Zika in humans. In this study, the insecticidal activity of 17 plant essential oils was evaluated via topical application against two strains of Ae. aegypti mosquito, Orlando (insecticide-susceptible) and Puerto Rico (pyrethroid-resistant). Initial screens with the Orlando strain showed that cucumber seed oil (2017 sample) was the most toxic, followed by sandalwood and thyme oil. When the essential oils were mixed with permethrin, they failed to show any significant synergism of insecticidal activity. Sandalwood and thyme oils displayed consistently high mortality against the resistant Puerto Rico strain, with low resistance ratios of 2.1 and 1.4, respectively. In contrast, cucumber seed oil showed significantly less activity against Puerto Rico mosquitoes, with a resistance ratio of 45. Bioactivity-guided fractionation of the 2017 sample of cucumber seed oil sample via flash column chromatography produced 11 fractions, and gas-chromatography/mass spectrometry analysis revealed that the three active fractions were contaminated with 0.33, 0.36, and 0.33% of chlorpyrifos-methyl, an organophosphorus insecticide, whereas inactive fractions did not show any trace of it. These results suggested that the insecticidal activity of cucumber seed oil was probably due to the presence of the insecticide, later confirmed with a clean batch of cucumber seed oil obtained in 2018, which showed negligible insecticidal activity. These findings demonstrate clearly the need for essential oil analysis to confirm purity before any claims are made about pesticidal potency.

Fungicidal Properties of Some Novel Trifluoromethylphenyl Amides.

Trifluoromethylphenyl amides (TFMPAs) were designed and synthesized as potential pesticides. Thirty-three structures were evaluated for fungicidal activity against three Colletotrichum species using direct bioautography assays. Active compounds were subsequently tested against C. fragariae, C. gloeosporioides, C. acutatum, Phomopsis obscurans, P. viticola, Botrytis cinerea and Fusarium oxysporum. The study identified 2-chloro-N-[2,6-dichloro-4-(trifluoromethyl)phenyl]acetamide (7a) as showing the strongest antifungal activity, and the broadest activity spectrum in this set against Colletotrichum acutatum (at 48 and 72 h) and Phomopsis viticola (at 144 h). The presence of triethylamine in its complex with N-[2,6-dichloro-4-(trifluoromethyl)phenyl]-2,2,3,3,3-pentafluoropropanamide (7b') played an important role in the bioactivity, and depending on the concentration or fungal species it showed higher or lower activity than the parent amide. X-Ray crystallography has shown that the complex (7b') is an ion pair, (C10 H2 Cl2 F8 NO)- (C6 H16 N)+ , where a proton is transferred from the amide nitrogen to the triethylamine nitrogen and then connected by hydrogen bonding to the acyl oxygen (N-H 0.893 Å; H⋅⋅⋅O 1.850 Å; N⋅⋅⋅O 2.711 Å; N-H⋅⋅⋅O 161.2(13)°). Although none of these compounds were better than standards, this work revealed some potential lead structures for further development of active novel compounds.

Vapor toxicity of five volatile pyrethroids against Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles quadrimaculatus (Diptera: Culicidae).

BACKGROUND: Mosquito mortality has been documented in numerous studies of spatial repellents but the concentration-dependent toxicity of spatial repellent vapors has not been documented. To address this issue, prallethrin, flumethrin, metofluthrin, transfluthrin, and meperfluthrin were selected for comparative study against Aedes albopictus (Skuse), Ae. aegypti (L.), Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say. Mosquito were exposed to vapors of each chemical for 2, 4, and 24 h with mortality recorded at each time point. A second experiment involved exposing mosquitoes to vapors for 2 h, then transferring them to untreated holding containers and held for 24 h. For these mosquitoes, readings were only taken after 24 h to allow for metabolic detoxification and recovery. RESULTS: LC50 and LC90 data indicated that transfluthrin and meperfluthrin had the greatest toxicity across all species, followed by metofluthrin, prallethrin, and flumethrin. CONCLUSION: Our findings, through the direct comparison of these compounds, suggest that transfluthrin, meperfluthrin, and metofluthrin be considered for further development. The vapor toxicity for the aforementioned compounds significantly exceeds prallethrin, which is currently market available as an adulticidal active ingredient in public health pest control. © 2018 Society of Chemical Industry.

Insecticidal and repellent properties of novel trifluoromethylphenyl amides II.

This project focused on the design, synthesis, and testing of trifluoromethylphenyl amides (TFMPAs) as potential mosquitocides and repellents. Fourteen compounds were evaluated for toxicity against larvae and adults of Aedes aegypti. Several compounds were toxic against Aedes aegypti (larval, adult and feeding bioassays) and Drosophila melanogaster (glass-surface contact assay), but were much less toxic than fipronil, with toxicity ratios ranging from 100-fold in the larval assay to 100,000-fold for topical application to adult insects. In repellency bioassays to determine minimum effective dosage (MED), compound N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,3,3,3-pentafluoropropanamide (7b) repelled Ae. aegypti females at lower concentration, 0.017 (±0.006) µmol/cm2, than N, N-diethyl-meta-toluamide (DEET) 0.026 (±0.005) µmol/cm2. 2-Chloro-N-(3-(trifluoromethyl)phenyl)acetamide (6a) performed better than DEET against two species of mosquitoes: it repelled Ae. aegypti females at 0.013 (±0.006) µmol/cm2 and Anopheles gambiae females (in a warm body repellent assay), at a standard exposure of 2 nmol/cm2. These studies revealed novel active structures that could further lead to compounds with better repellent activity.

Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner.

Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

Lantana montevidensis Essential Oil: Chemical Composition and Mosquito Repellent Activity against Aedes aegypti.

The essential oil (EO) of Lantana montevidensis (Spreng.) Briq. (L. sellowiana Link & Otto) was investigated for its chemical composition and mosquito repellent activity. The essential oil obtained by hydrodistillation of aerial plant parts was analyzed by GC-FID and GC-MS. The major constituents were p-elemene (22.0%), ß-caryophyllene (20.1%), and germacrene D (9.4%). Sesquiterpene hydrocarbons were present.in considerable quantities (78.9%) in the L. montevidensis EO, followed by oxygenated sesquiterpenes (8.9%), monoterpene hydrocarbons (7.7%), oxygenated monoterpenes (1.9%), diterpenes (1.2%) and other compounds (0.2%). The oil of L. montevidensis was repellent with a minimum effective dosage (MED) of 0.021 ± 0.013 mg/cm(2) as compared with that of the positive control N,N-diethyl-3-methylbenzamide (DEET) with a MED of 0.006 : 0.001 mg/cm(2)) against Aedes aegypti L. The major compound ß-elemene was tested individually for its repellency and had a MED value of 0.23 ? 0.14 mg/cm2 (DEET was 0.008 ? 0.001 mg/cm2). This is the first report on the repellent activity of L. montevidensis EO and P-elemene using human-based in vivo assays against Ae. aegypti.

Comparison of Volatiles and Mosquito Capture Efficacy For Three Carbohydrate Sources In A Yeast-Fermentation CO2 Generator.

Mosquito surveillance in remote areas with limited access to canisters of CO2 or dry ice will benefit from an effective alternative CO2 source, such as the natural production of CO2 from yeast fermentation. In this study, we investigate differences in mosquito capture rates from the Centers for Disease Control and Prevention (CDC) light traps baited with dry ice compared with traps baited with yeast fermentation of several carbohydrate sources over 23 trap-nights. Results demonstrated the ability of yeast-generated CO2 to effectively attract mosquitoes to a CDC trap, regardless of carbohydrate source. Total collections of mosquitoes using dry ice were significantly higher than collections from yeast-generated CO2 sources. However, mosquito community structure, i.e., the species and relative capture rate of each species, was represented comparably across collections regardless of CO2 source. Volatiles produced by yeast fermentation were analyzed by carbohydrate source, revealing a suite of compounds, possibly synergistic, enhancing effects with CO2 on mosquito collection capability compared with the amount of CO2 used to attract mosquitoes.

Promising Aedes aegypti repellent chemotypes identified through integrated QSAR, virtual screening, synthesis, and bioassay.

Molecular field topology analysis, scaffold hopping, and molecular docking were used as complementary computational tools for the design of repellents for Aedes aegypti, the insect vector for yellow fever, chikungunya, and dengue fever. A large number of analogues were evaluated by virtual screening with Glide molecular docking software. This produced several dozen hits that were either synthesized or procured from commercial sources. Analysis of these compounds by a repellent bioassay resulted in a few highly active chemicals (in terms of minimum effective dosage) as viable candidates for further hit-to-lead and lead optimization effort.

Phoenix dactylifera L. spathe essential oil: chemical composition and repellent activity against the yellow fever mosquito.

Date palm, Phoenix dactylifera L. (Arecaceae), grows commonly in the Arabian Peninsula and is traditionally used to treat various diseases. The aim of the present study was to identify chemical composition of the essential oil and to investigate the repellent activity. The essential oil of P. dactylifera was obtained by hydrodistillation from the spathe, a specialized leaf structure that surrounds the pollinating organs of the palm. The oil was subsequently analyzed by GC-FID and GC-MS. The oil showed promising repellent activity against yellow fever mosquito - Aedes aegypti. Sixteen components were characterized, constituting 99% of the oil. The main components were 3,4-dimethoxytoluene (73.5%), 2,4-dimethoxytoluene (9.5%), ß-caryophyllene (5.5%), p-cresyl methyl ether (3.8%), and caryophyllene oxide (2.4%). The minimum effective dosage (MED) for repellency for the P. dactylifera oil was 0.051mg/cm(2), which had moderately lower potency compared to reference standard N,N-diethyl-3-methylbenzamide, DEET (0.018mg/cm(2)) in the "cloth patch assay". The five major compounds were individually assayed for repellency to determine to what extent each is responsible for repellency from the oil. 3,4-Dimethoxytoluene and 2,4-dimethoxytoluene showed the best repellent activity with the same MED value of 0.063mg/cm(2), respectively. The results indicate that these two constituents which comprise a large proportion of the P. dactylifera oil (83%) are likely responsible for the observed repellent activity. In this aspect, the P. dactylifera spathe oil is a sustainable, promising new source of natural repellents.

Chemical composition, antifungal and insecticidal activities of Hedychium essential oils.

The antimicrobial properties of essential oils have been documented, and their use as "biocides" is gaining popularity. The aims of this study were to analyze the chemical composition and assess the biological activities of Hedychium essential oils. Oils from 19 Hedychium species and cultivars were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. The antifungal and insecticidal activities of these oils were tested against Colletotrichum acutatum, C. fragariae, and C. gloeosporioides, and three insects, the azalea lace bug (Stephanitis pyrioides), the yellow fever mosquito (Aedes aegypti), and the red imported fire ant (Solenopsis invicta). Hedychium oils were rich in monoterpenes and sesquiterpenes, especially 1,8-cineole (0.1%-42%), linalool (<0.1%-56%), a-pinene (3%-17%), b-pinene (4%-31%), and (E)-nerolidol (0.1%-20%). Hedychium oils had no antifungal effect on C. gloeosporioides, C. fragariae, and C. acutatum, but most Hedychium oils effectively killed azalea lace bugs. The oils also show promise as an adult mosquito repellent, but they would make rather poor larvicides or adulticides for mosquito control. Hedychium oils acted either as a fire ant repellent or attractant, depending on plant genotype and oil concentration.

Biting deterrence, repellency, and larvicidal activity of Ruta chalepensis (Sapindales: Rutaceae) essential oil and its major individual constituents against mosquitoes.

The essential oil from aerial parts of Ruta chalepensis L. (Sapindales: Rutaceae) was obtained by hydrodistillation, and its chemical profile was identified using gas chromatography and gas chromatography-mass spectrometry. Compounds, 2-undecanone (43.2%), 2-nonanone (27.9%), and 2-nonyl acetate (10.6%) were the major constituents of the oil. Biting deterrent activity of R. chalepensis essential oil at 10 and 50 microg/cm2, 2-undecanone at 8.5 microg/cm2, 2-nonanone at 9 microg/cm2, and 2-nonyl acetate at 9.3 microg/cm2 was similar to DEET (N, N-diethyl-meta-toluamide) at 4.8 microg/cm2, against Aedes aegypti L. Biting deterrent activity of R. chalepensis oil at 50 microg/cm2 against Anopheles quadrimaculatus Say was statistically similar to DEET at 4.8 microg/cm2, whereas the activity was lower in the other compounds tested. In cloth patch assay, R. chalepensis essential oil was effective at 187 microg/cm2, whereas 2-undecanone was effective at 108.9 microg/cm2 against Ae. aegypti. In larval bioassays, 2-undecanone showed similar toxicity whereas toxicity of R. chalepensis essential oil and 2-nonanone was higher at 24-h posttreatment at the LD50 in An. quadrimaculatus than Ae. aegypti. This study revealed that R. chalepensis essential oil and its major compounds were active biting deterrents against Ae. aegypti at higher application rates whereas only the essential oil showed activity similar to DEET against An. quadrimaculatus. 2-undecanone was the most active compound in in vivo repellency bioassay against Ae. aegypti. Chemical composition of R. chalepensis essential oil varies because of plant production and harvest practices, and the activity level of the essential oil may depend on the source of the sample.

Insecticidal, repellent and fungicidal properties of novel trifluoromethylphenyl amides.

Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC50 1940 nM), while against adults N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide (1c) was most active (24 h LD50 19.182 nM, 0.5 µL/insect). However, the 24 h LC50 and LD50 values of fipronil against Ae. aegypti larvae and adults were significantly lower: 13.55 nM and 0.787 × 10(-4) nM, respectively. Compound 1c was also active against Drosophila melanogaster adults with 24 h LC50 values of 5.6 and 4.9 µg/cm(2) for the Oregon-R and 1675 strains, respectively. Fipronil had LC50 values of 0.004 and 0.017 µg/cm(2) against the two strains of D. melanogaster, respectively. In repellency bioassays against female Ae. aegypti, 2,2,2-trifluoro-N-(2-(trifluoromethyl)phenyl)acetamide (4c) had the highest repellent potency with a minimum effective dosage (MED) of 0.039 µmol/cm(2) compared to DEET (MED of 0.091 µmol/cm(2)). Compound N-(2-(trifluoromethyl)phenyl)hexanamide (4a) had an MED of 0.091 µmol/cm(2) which was comparable to DEET. Compound 4c was the most potent fungicide against Phomopsis obscurans. Several trends were discerned between the structural configuration of these molecules and the effect of structural changes on toxicity and repellency. Para- or meta- trifluoromethylphenyl amides with an aromatic ring attached to the carbonyl carbon showed higher toxicity against Ae. aegypti larvae, than ortho- trifluoromethylphenyl amides. Ortho- trifluoromethylphenyl amides with trifluoromethyl or alkyl group attached to the carbonyl carbon produced higher repellent activity against female Ae. aegypti and Anopheles albimanus than meta- or para- trifluoromethylphenyl amides. The presence of 2,6-dichloro- substitution on the phenyl ring of the amide had an influence on larvicidal and repellent activity of para- trifluoromethylphenyl amides.

Cyclohexanol analogues are positive modulators of GABA(A) receptor currents and act as general anaesthetics in vivo.

GABA(A) receptors meet all the pharmacological criteria required to be considered important general anaesthetic targets. In the following study, the modulatory effects of various commercially available and novel cyclohexanols were investigated on recombinant human γ-aminobutyric acid (GABA(A), α(1)ß(2)γ(2s)) receptors expressed in Xenopus oocytes, and compared to the modulatory effects on GABA currents observed with exposures to the intravenous anaesthetic agent, propofol. Submaximal EC(20) GABA currents were typically enhanced by co-applications of 3-300 µM cyclohexanols. For instance, at 30 µM 2,6-diisopropylcyclohexanol (a novel compound) GABA responses were increased ~3-fold (although similar enhancements were achieved at 3 µM propofol). As regards rank order for modulation by the cyclohexanol analogues at 30 µM, the % enhancements for 2,6-dimethylcyclohexanol~2,6-diethylcyclohexanol~2,6-diisopropylcyclohexanol~2,6-di-sec-butylcyclohexanol ≫2,6-di-tert-butylcyclohexanol~4-tert-butylcyclohexanol>cyclohexanol~cyclopentanol~2-methylcyclohexanol. We further tested the potencies of the cyclohexanol analogues as general anaesthetics using a tadpole in vivo assay. Both 2,6-diisopropylcyclohexanol and 2,6-dimethylcyclohexanol were effective as anaesthetics with EC(50)s of 14.0 µM and 13.1 µM respectively, while other cyclohexanols with bulkier side chains were less potent. In conclusion, our data indicate that cyclohexanols are both positive modulators of GABA(A) receptors currents and anaesthetics. The positioning and size of the alkyl groups at the 2 and 6 positions on the cyclohexanol ring were critical determinants of activity.

Novel carboxamides as potential mosquito repellents.

A model was developed using 167 carboxamide derivatives, from the United States Department of Agriculture archival database, that were tested as arthropod repellents over the past 60 yr. An artificial neural network employing CODESSA PRO descriptors was used to construct a quantitative structure-activity relationship model for prediction of novel mosquito repellents. By correlating the structure of these carboxamides with complete protection time, a measure of repellency based on duration, 34 carboxamides were predicted as candidate mosquito repellents. There were four additional compounds selected on the basis of their structural similarity to those predicted. The compounds were synthesized either by reaction of 1-acylbenzotriazoles with secondary amines or by reaction of acid chlorides with secondary amines in the presence of sodium hydride. The biological efficacy was assessed by duration of repellency on cloth at two dosages (25 and 2.5 micromol/cm2) and by the minimum effective dosage to prevent Aedes aegypti (L.) (Diptera: Culicidae) bites. One compound, (E)-N-cyclohexyl-N-ethyl-2-hexenamide, was superior to N,N-diethyl-3-methylbenzamide (deet) at both the high dosage (22 d versus 7 d for deet) and low dosage (5 d versus 2.5 d for deet). Only one of the carboxamides, hexahydro-1-(l-oxohexyl)-1H-azepine, had a minimum effective dosage that was equivalent or slightly better than that of deet (0.033 micromol/cm2 versus 0.047 micromol/cm2).

Eupatorium capillifolium essential oil: chemical composition, antifungal activity, and insecticidal activity.

Natural plant extracts often contain compounds that are useful in pest management applications. The essential oil of Eupatorium capillifolium (dog-fennel) was investigated for antifungal and insecticidal activities. Essential oil obtained by hydrodistillation of aerial parts was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The major components were determined to be thymol methyl ether (=methyl thymol) (36.3%), 2,5-dimethoxy-p-cymene (20.8%) and myrcene (15.7%). Antifungal activity of the essential oil was weak against the plant pathogens Colletotrichum acutatum, C. fragariae, and C. gloeosporioides in direct bioautography assay. The E. capillifolium oil showed promising repellent activity against the yellow fever mosquito Aedes aegypti, whereas the oil exhibited moderate activity against the mosquito's first instar larvae in a high throughput bioassay. Topical applications of the oil showed no activity against the blood-feeding female adults of A. aegypti. Eupatorium capillifolium essential oil showed a linear dose response between adult lace bug (Stephanitis pyrioides) mortality and increasing oil concentration in an adulticidal activity bioassay. The dog-fennel oil was more potent than the conventional insecticide malathion. In conclusion, these combined results showed Eupatorium capillifolium oil is a promising novel source of a biological insecticide with multiple modes of action.

Synthesis and characterization of a redox-active ion channel supporting cation flux in lipid bilayers.

The synthesis, cation binding and transmembrane conductive properties of a novel synthetic ion channel containing a redox-active ferrocene unit are described. Fluorescence spectroscopy was used to demonstrate that the channel supports multiple ion coordination and association constants for 1:1 and 1:2 (channel:cation) coordination for both Na(+) and K(+) were evaluated. Experiments using a black lipid membrane preparation revealed that this compound functioned effectively as an ion channel for both Na(+) and K(+). Concomitant (23)Na NMR spectroscopy studies supported this finding and revealed a Na(+) flux, at least 5 times higher than ion transport rates by monensin. Furthermore, oxidation of the redox-active centre (Fe(2+) to Fe(3+)) effectively inhibited ion transport.