Commercial Repellent Research Articles

A Comprehensive Review on Insect Repellent Agents: Medicinal Plants and Synthetic Compounds.

Plant-based repellents have been used for generations as personal protection against mosquitoes. Ethnobotanical studies provide valuable knowledge for developing natural prod-ucts. Commercial repellents with plant-based ingredients are popular, but insufficient studies follow Pesticide Evaluation Scheme WHO guidelines. Further standardized studies are needed to evaluate repellent compounds and develop high-repellency and safe products. Essential Oils (EOs) from aromatic plants have gained popularity as low-risk insecticides due to their low toxicity and short environmental persistence. These plant-derived EOs, produced through steam distillation, have repellent, insecticidal, and growth-reducing effects on various insects. They control phytophagous insects, bite flies, and home and garden insects. US registration is the main hurdle for new EOs. This review explores the use of essential oils from plants as a natural repellent, focusing on their effectiveness and synergistic effects. Essential oils are vol-atile mixtures of hydrocarbons with diverse functional groups, and their effectiveness is linked to monoterpenes and sesquiterpenes. Synergistic effects can improve their effectiveness, and the use of other natural products, like vanillin, can increase protection time. Cymbopogon spp., Ocimum spp., and Eucalyptus spp. are among the most promising plant families.

A Simple Model to Study Mosaic Gene Expression in 3D Endothelial Spheroids.

The goal of this study was to establish a simple model of 3D endothelial spheroids with mosaic gene expression using adeno-associated virus (AAV) transduction, with a future aim being to study the activity of post-zygotic mutations common to vascular malformations. In this study, 96-well U-bottom plates coated with a commercial repellent were seeded with two immortalized human endothelial cell lines and aggregation monitored using standard microscopy or live-cell analysis. The eGFP expression was used to monitor the AAV transduction. HUVEC-TERT2 could not form spheroids spontaneously. The inclusion of collagen I in the growth medium could stimulate cell aggregation; however, these spheroids were not stable. In contrast, the hCMEC/D3 cells aggregated spontaneously and formed reproducible, robust 3D spheroids within 3 days, growing steadily for at least 4 weeks without the need for media refreshment. The hCMEC/D3 spheroids spontaneously developed a basement membrane, including collagen I, and expressed endothelial-specific CD31 at the spheroid surface. Serotypes AAV1 and AAV2QUADYF transduced these spheroids without toxicity and established sustained, mosaic eGFP expression. In the future, this simple approach to endothelial spheroid formation combined with live-cell imaging could be used to rapidly assess the 3D phenotypes and drug and radiation sensitivities arising from mosaic mutations common to brain vascular malformations.

Evaluating deterrents to reduce depredation of wood duck eggs in nest boxes

AbstractWood ducks (Aix sponsa) are secondary natural cavity‐nesting species that also nest in artificial nest boxes. Since the early 20th century, nest boxes have been widely deployed in North America to increase nesting sites for wood ducks and bolster production. Equipping nest boxes with a predator guard beneath the box is a common practice to deter climbing predators from accessing boxes; however, there is no device to repel avian predators. We found that eastern rat snakes (Pantherophis alleghaniensis) and woodpeckers (Picidae) were primary predators of wood duck eggs in boxes in North Carolina and South Carolina. Accordingly, we designed experiments to deter snakes and woodpeckers using a commercial brand of snake repellent pellets and a plastic raptor decoy, respectively. Male and female snakes that accessed boxes averaged 1.4 m (SE = 2.0 cm) in length. Digital camera data indicated that snakes climbed nest box posts and thrust their anterior body atop predator guards to continue their ascent into the box. We recorded 671 nest failures of which rat snakes accounted for 39.9% (n = 268) and woodpeckers 22.4% (n = 150). Snakes consumed ≥649 eggs, observed as protuberances in their stomachs. Our experiment showed that commercial snake repellent pellets did not deter snakes (P = 0.957). Placing a plastic hawk decoy atop nest boxes when females were incubating ≥12 days increased nest survival during the incubation stage (P = 0.001). Wood duck nest boxes at our study sites may be experiencing increased nest predation by rat snakes due to poor maintenance and installation of predator guards. Rat snakes and woodpeckers may be depredating wood duck eggs in the southeastern United States at unknown rates, potentially decreasing production and recruitment from these structures.

Tick repellent activities of supercritical fluid extract from Chamaecyparis obtusa against Haemaphysalis longicornis

Supercritical fluid extraction (SFE) is a rapid, selective, and convenient method for sample preparation prior to the analysis of compounds in a volatile product of plant matrices. In this study, insecticidal activity and repellency were examined in a laboratory study to determine the active constituent of Chamaeparis obtusa and a supercritical fluid extract from Chamaeparis obtusa against hard tick Haemaphysalis longicornis.The repellency of C. obtusa oil was evaluated in comparison with two commercial repellents (Icaridin and DEET) against H. longicornis. Filter-paper diffusion assay revealed that C. obtusa oil (3.2 µg/cm2) had a 100 % repellency and icaridine (3.2 µg/cm2) had a 96.1 % repellency at 120 min. Repellencies of 31 compounds against H. longicornis were compared with the repellency of DEET at 3.2 µg/cm2. Responses varied according to the test compound and exposure time. Repellencies of α-terpinene, terpinene-4-ol, and α-terpineol were 100 % at 30 min post-treatment. They were 85.5 %, 56.4 %, and 68.9 %, respectively, at 120 min. C. obtusa oil, α-terpinene, terpinene-4-ol, and α-terpineol merit further study as potential fumigants or lead compounds for the control of H. longicornis.

Development and evaluation of test methods for commercial spatial repellent products using the common fruit flies in laboratory and simulated-use scenarios

Fruit flies and other miniscule flying insects often cause a nuisance in the kitchen areas of our dwellings. To mitigate the invasion of indoor insect pests, behavioral modifications using spatial repellents containing natural products are emerging as alternatives to chemical insecticides especially around the kitchens and food storage areas. However, the absence of standardized testing methods for spatial repellency has undermined the reliability of these products. We introduced three distinct laboratory-scale repellency assays and their relevancy to simulated-use conditions. Out of eleven commercial products tested, five showed effectiveness in laboratory assays, and three of these were further proven effective in simulated-use tests as well. Another issue limiting the utility of commercially available spatial repellents was the lack of clear and comprehensive use instructions on product labels, potentially leading to ineffective applications. We observed that increasing the applied quantity improved the efficacy of one product that was initially determined to be ineffective in a simulated-use test. Based on our findings, we propose three strategies for regulations of spatial repellents: 1) consideration of mixture effects beyond single active ingredients especially using the natural products as their active ingredients, 2) the use of multiple testing systems, while acknowledging the limitations of laboratory assays in predicting real-world efficacy, and 3) ensuring product labels provide detailed and clear instructions for effective use.

Block copolymers hybrid latex coatings with environment-friendly short-chain perfluoroalkyl: From sequence structure to surface properties

Block copolymers (BCs) of perfluorocarbons (PFCs) show a well-ordered phase separation morphology on the surface that is an ideal structure to fabricate low surface free energy (SFE) environment-friendly short-chained PFCs based coating materials. In this study, a series of block copolymers of 2-(perfluorobutyl) ethyl acrylate hybrid latex coating materials were synthesized via soap-free RAFT emulsion polymerization. The impact of copolymers sequence structure on the surface properties and surface micro-nano structure of hybrid latex films were investigated. The results revealed that the functional chain segments of short-chain perfluorinated were preferentially arranged in the outermost chain segments of the BCs, thereby leading to the stacking of trifluoromethyl (-CF3) groups on the hybrid latex film surfaces and the decrease of SFE. The SFE of BCs latex films were significantly reduced from 21.83 mN/m to 16.03 mN/m compared to that of the random copolymer. Additionally, the SFE of the hybrid latex film can be reduced to 15.32 mN/m under the action of the modified silica crosslinking. Ultimately, the hybrid latex films show excellent superhydrophobic and oleophobic properties on cotton fabrics with water and oil contact angles of 152.5° and 142.4°, respectively, reaching the level of commercial water and oil repellent finishing agents with six fluorocarbon atoms. This study of BCs hybrid latex coatings provides important insights into the mechanism of the sequence structure and surface properties of BCs and offers an environment-friendly superhydrophobic and oleophobic coating material.

Harmful and Harmless Soil-Dwelling Fungi Indicate Microhabitat Suitability for Off-Host Ixodid Ticks.

Following blood meals or questing bouts, hard ticks (Ixodidae) must locate moist off-host microhabitats as refuge. Soil-dwelling fungi, including entomopathogenic Beauveria bassiana (Bb), thrive in moist microhabitats. Working with six species of ixodid ticks in olfactometer bioassays, we tested the hypothesis that ticks avoid Bb. Contrary to our prediction, nearly all ticks sought, rather than avoided, Bb-inoculated substrates. In further bioassays with female black-legged ticks, Ixodes scapularis, ticks oriented towards both harmful Bb and harmless soil-dwelling fungi, implying that fungi-regardless of their pathogenicity-signal habitat suitability to ticks. Only accessible Bb-inoculated substrate appealed to ticks, indicating that they sense Bb or its metabolites by contact chemoreception. Bb-inoculated substrate required ≥24 h of incubation before it appealed to ticks, suggesting that they respond to Bb metabolites rather than to Bb itself. Similarly, ticks responded to Bb-inoculated and incubated cellulose but not to sterile cellulose, indicating that Bb detection by ticks hinges on the Bb metabolism of cellulose. 2-Methylisoborneol-a common fungal metabolite with elevated presence in disturbed soils-strongly deterred ticks. Off-host ticks that avoid disturbed soil may lower their risk of physical injury. Synthetic 2-methylisoborneol could become a commercial tick repellent, provided its repellency extends to ticks in diverse taxa.

Designing thermoreversible gels for extended release of mosquito repellent.

Mosquito-borne diseases are responsible for 700 000 deaths annually. Current outdoor protective strategies primarily focus on direct skin application of commercial repellents (i.e., aerosol sprays or topical lotions) which are typically limited to efficacy times of ≤10 hours due to rapid evaporation and dermal absorption. Consequently, frequent reapplication for continuous protection can increase associated health hazards and cause noncompliance. This study utilizes Hansen solubility parameter modeling to design physical gels composed of insect-repelling N,N-diethyl-meta-toluamide (DEET) and modacrylic copolymer poly(acrylonitrile-co-vinyl chloride) (P(AN-VC)). The P(AN-VC)/DEET composites exhibit tunable and reversible sol-gel transition temperatures that can meet the thermomechanical stability demands of the intended application and permit facile transition to commercial melt processing techniques such as injection molding, filament spinning, or film casting. P(AN-VC)/DEET gel films demonstrate mosquito repellency for more than half a year-performing longer than any other known material to date-due to the high reservoir of repellent and its desorption hindrance from the polymer matrix. Therefore, P(AN-VC)/DEET gels hold significant potential for extended protection against mosquitos and other biting arthropods.

Phytochemical Profiles and Mosquito-Repellent Properties of Indigenous Plants from Pak Panang District, Nakhon Si Thammarat, Thailand

This study investigated the mosquito-repelling ability of folkloric indigenous plants by phytochemical extraction using three distinct methods. The phytochemical composition and antioxidant activities of the extracts were evaluated using thin-layer chromatography. The average powder weights of Citrus maxima (CM), Eleocharisdulcis plantaginea (EP), and Thespesia populnea (TP) were 154.33, 156.67, and 153.78 mg/g dry weight, respectively, and are substantially different from the other ten species (p=0.05). However, this technique did not affect the extract yield. The region of interest (ROI) values for the antioxidant activity of these three species were 328.9, 924.0, and 735.0, respectively. The repellent activities of the CM, TP, and EP extracts were significantly lower than those of DEET; however, the repellent activities of the mixed extract did not differ (p=0.05). This study found that indigenous plants commonly used in the region have mosquito-repellant and antioxidant properties. Combining the three extracts would yield the same activity as DEET, an ingredient used in commercial mosquito repellents.

Do Commercial Insect Repellents Provide Protection against the Tick Amblyomma sculptum (Acari: Ixodidae)?

Amblyomma sculptum is a species of public health interest because it is associated with the transmission of the bacteria that causes Brazilian Spotted Fever (BSF). The use of repellents on humans is a prophylactic measure widely used to provide protection against a series of arthropod vectors, including mosquitoes and ticks. However, in Brazil, the effectiveness of commercial repellents against A. sculptum is little known. Therefore, it is necessary to carry out specific studies to evaluate the repellency of these commercial products, registered for use against mosquitoes, against the star tick. The main goal of the present work was to evaluate the effectiveness of six commercial repellents against A. sculptum. Unfed nymphs, aged between two and eight weeks, were tested against products based on DEET (OFF!® and Repelex®), Icaridin (Exposis® and SBP®), and IR3535 (Johnsons and Henlau). Three bioassays were conducted to evaluate tick behavior: (i) filter paper, (ii) fingertip, and (iii) field. All bases tested showed high repellent activity, differing significantly (p < 0.05) from the control. It was observed the formulation with DEET resulted in the best results in the filter paper bioassay. In the fingertip bioassay, the DEET base repelled a greater number of ticks compared to Icaridin. In the field bioassay, there was no significant difference between the Icaridin base and DEET, and both formulations differed from the control (p < 0.05). The six formulations tested showed significant percentages of repellency against ticks; however, for the fingertip and field bioassays, the products OFF!®, Repelex®, and Exposis® were tested as they showed better performance in the filter paper test. OFF!® showed the best percentage of repellency (100%), followed by Repelex® (96.8%), and Exposis® (93.1%), considering the two-hour period of the bioassay-field-test. Proving the effectiveness of repellents on the market against A. sculptum presented in this study is crucial, since this is the main ectoparasite of humans that can transmit Rickettsia rickettsii when infected. The effectiveness of commercial insect repellents against other tick species that parasitize humans can also be explored.

Prolonged Repellent Activity of Plant Essential Oils against Dengue Vector, Aedes aegypti.

Repellents are effective personal protective means against outdoor biting mosquitoes. Repellent formulations composed of EOs are finding increased popularity among consumers. In this study, after an initial screening of 11 essential oils (EOs) at the concentration of 33 μg/cm2, five of the most repellent EOs, Perovskia atriplicifolia, Citrus reticulata (fruit peels), C. reticulata (leaves), Mentha longifolia, and Dysphania ambrosioides were further investigated for repellent activity against Aedes aegypti mosquitoes in time span bioassays. When tested at the concentrations of 33 μg/cm2, 165 μg/cm2 and 330 μg/cm2, the EO of P. atriplicifolia showed the longest repellent effect up to 75, 90 and 135 min, respectively, which was followed by C. reticulata (peels) for 60, 90 and 120 min, M. longifolia for 45, 60 and 90 min, and C. reticulata (leaves) for 30, 45 and 75 min. Notably, the EO of P. atriplicifolia tested at the dose of 330 μg/cm2 showed complete protection for 60 min which was similar to the commercial mosquito repellent DEET. Gas chromatographic-mass spectrometric analyses of the EOs revealed camphor (19.7%), limonene (92.7%), sabinene (24.9%), carvone (82.6%), and trans-ascaridole (38.8%) as the major constituents of P. atriplicifolia, C. reticulata (peels), C. reticulata (leaves), M. longifolia, and D. ambrosioides, respectively. The results of the present study could help develop plant-based commercial repellents to protect humans from dengue mosquitoes.

Cyclic Acetals as Novel Long-Lasting Mosquito Repellents.

The use of skin repellents against hematophagous mosquitoes is an important personal protection practice wherever these insects are abundant and where they are vectors of diseases. DEET and Icaridin are the major synthetic insect repellents in commercial formulations and are considered the most effective. Here, we tested against the mosquito Aedes albopictus several cyclic hydroxyacetals synthesized by acetalization of commercially available aliphatic carbonyl compounds (ranging from C3 to C15) with either glycerol, 1,1,1-trismethyloletane, or 1,1,1-trismethylolpropane and compared their efficacy with commercial repellents. We found that several hydroxyacetals were comparable with DEET and Icaridin both in terms of the required dose and repellence duration, while a few performed better. For those most active, toxicity was investigated, finding that a few of them were less cytotoxic than DEET and less prone to permeate through cell layers. Therefore, such results indicate that novel safe mosquito repellents could be developed among cyclic hydroxyacetals.

천연 진드기기피제 개발을 위한 블렌딩 에센셜오일의 진드기 기피효능에 관한 연구

In this study, an experiment was conducted to measure the tick repellent efficacy through the synergy effect according to the type and ratio of blending essential oil. The subjects were adults and nymphs of the Haemaphysalis longicornis, and the repellent efficacy was measured using the filter paper bioassay method. Based on the past research, citronella oil, geranium oil, vetiver oil, and neem oil were selected as a single treatment experiment since their repellent efficacy was confirmed. The first experiment revealed that the repellent efficacy of citronella oil and geranium oil were high. Afterwards, in order to investigate the synergy effect on tick repellent efficacy, experimental group was consisted of neem seed oil (carrier oil) that was blended with citronella and geranium oil, at a ratio of 1:1, 2:1, and 17:3 (15%). Also, negative control group was composed of ethanol that was blended with citronella and geranium oil at the same ratio of experimental group. As a result, the blending of citronella and neem seeds showed higher repellent efficacy in all blending ratios than the blending of geranium and neem seeds. In adult ticks, blending ratio of citronella and neem seeds was 1:1 and 17:3, showed the most significant difference of repellent efficacy. In nymph ticks, when the blending ratio of citronella and neem seed was 1:1 and 17:3, the repellent efficacy was the same as that of the positive control commercial repellent. In conclusion, it was confirmed that both nymph and adults ticks showed higher repellent efficacy when blended than single treatment. In this study, the synergy effect of the blending of citronella and neem seeds on the tick repellent effect has a high potential to replace synthetic repellents.

Differentiation of action mechanisms between natural and synthetic repellents through neuronal electroantennogram and proteomic in Aedes aegypti (Diptera: Culicidae)

Natural-based compounds with repellent activity arise nowadays with the possibility to replace commercial synthetic repellents wholly or partially, such as N,N-Diethyl-m-toluamide (DEET). It is due to DEET's demonstrated toxicity and cutaneous irritation for human beings. Besides, research recommends avoiding using it with kids and pregnant women. The search for a repellent product implies early stages of detailed research that resolve the modes of action against the target insect. Therefore the objective of the current study was to analyze neuronal electrophysiological signals and olfactory system protein expression when the Aedes aegypti mosquito with exposition to natural-based repellents. Adult females of Ae. aegypti of Rockefeller strain were exposed to specific concentrations of repellent compounds like geranyl acetate, α-bisabolol, nerolidol, and DEET. The neuronal effect was measured by electroantennography technique, and the effect of exposure to either DEET or a mixture of natural molecules on protein expression was determined with 2D-PAGE followed by MALDI-TOF-mass spectrometry (MS). This approach revealed that DEET affected proteins related to synapses and ATP production, whereas natural-based repellents increased transport, signaling, and detoxification proteins. The proteomic and electrophysiology experiments demonstrated that repellent exposure disrupts ionic channel activity and modifies neuronal synapse and energy production processes.

Mosquito Repellents: Efficacy Tests of Commercial Skin-Applied Products in China.

As a prevention tool for mosquito-borne diseases, mosquito repellents have received substantial attention. To make a convincing recommendation for repellent products to Chinese consumers, we compared the protection time (landing time and probing time) of the 26 best-selling commercial repellents in the Chinese market in a controlled laboratory environment. The data were analyzed by one-way ANOVA. Meanwhile, prices and favorable rates of repellents are also taken into consideration. In our study, N, N-diethyl-m-toluamide (DEET)-based products provided the longest protection time (0.5–3.88 h landing time and/or 1–5.63 h probing time) and lower prices (13.9–21.9 yuan) than other components (ethyl butylacetylaminopropionate (IR3535), picaridin, and botanical. Among the 26 selected products, only 17 repellents showed repellency, and the best repellent was Green Jungle (15% DEET), with a mean (±SD) landing and/or probing time of 3.88 ± 1.65 h and/or 5.63 ± 0.36 h. For botanicals, only ICE King, OMNIbaby, and Ren He showed a little repellency. Autan (20% picaridin) performed best in the picaridin group. Run Ben (7% IR3535) stood out from the IR3535 group. In conclusion, DEET repellent is highly recommended to consumers. The combination of botanicals and synthesized chemicals is a new prospect for eco-friendly repellents.

Reducing Energy Consumption and Health Hazards of Electric Liquid Mosquito Repellents through TinyML.

Two problems arise when using commercially available electric liquid mosquito repellents. First, prallethrine, the main component of the liquid repellent, can have an adverse effect on the human body with extended exposure. Second, electricity is wasted when no mosquitoes are present. To solve these problems, a TinyML-oriented mosquito sound classification model is developed and integrated with a commercial electric liquid repellent device. Based on a convolutional neural network (CNN), the classification model can control the prallethrine vaporizer to turn on only when there are mosquitoes. As a consequence, the repellent user can avoid inhaling unnecessarily large amounts of the chemical, with the added benefit of dramatically reduced energy consumption by the repellent device.

Evaluation of quality and safety parameters of DEET commercial repellents: photostability, penetration/permeation and eye irritation studies

N',N'-diethyl-m-toluamide (DEET) is the repellent most commonly used against mosquito vectors of diseases such as dengue, yellow fever and chikungunya. In Brazil, DEET is marketed in aerosol, solution, lotion and gel forms, at concentrations ranging from 6.65 to 25%. In this study, the kinetic degradation under UVC radiation was studied, as well as the penetration/permeation and the ocular irritant potential of DEET repellents in the form of solution, lotion and gel. The photostability study was conducted over 96h, and the DEET degradation kinetics under UVC radiation was fitted to the zero-order model for the three formulations; t90% values of 23.7 h, 17.0 h and 16.1 h were obtained for gel, lotion and solution forms, respectively. The in vitro skin penetration/permeation using the vertical Franz cell in pig skin showed that all the formulations penetrated/permeated the skin layers, at a higher rate when the lotion (p&lt;0.05) was used, possibly due to its qualitative composition. The in vitro ocular irritant potential using the HET-CAM method indicated that one of the products evaluated was classified as "moderate irritant" and five as "severe irritant”. The set of data indicated the lower penetration/permeation of the solution form and reinforces the importance of being careful during application, to avoid accidental contact with the eyes.

Developing ecofriendly sambrani and mosquito repellent using elephant dung

India is one of the largest Sambrani-producing countries. Sambrani, a globally traded product, is burnt for fragrance. According to Bordoloi & Sharma (2007) [5] approximately, a revenue of Rupees 7.1 billion comes from the total domestic sales of Sambrani. In India significantly, about two-thirds of the domestic usage of sambrani takes place in rural areas (61.23%). Elephant dung is rich in fiber content which makes it as a suitable raw material for manufacturing mosquito repellant and sambrani. Mosquitoes are the most vital carrier of viral diseases in the urban, suburban and rural environments. They are the primary carriers of dengue, malaria, and several other diseases that may even lead to pandemic. Hence, a eco-friendly sambrani and mosquito Repellent Formulation was designed using elephant dung. The burning ability such as initial burning, final burning, flammability, time interval and ash content were recorded for sambrani. Natural ingredients like Tulsi, Neem leaves, Lemon grass oil and Natural gum were used in combination with the elephant dung to reinforce the potency of the mosquito repellent. Smoke toxicity of organic mosquito repellent was evaluated. Emission test for commercial and formulated repellent was also carried out and compared, and it is evident that there is 57% reduction in the carbon-di-oxide emission from formulated repellent than commercial repellent and there are no traces of emission of carbon monoxide from the repellent. This formulation is safe, eco-friendly, cheap, easy to use, and has maximum repellence against mosquitoes. Production of these natural repellents with elephant dung may help to increase the livelihood security of rural poor/tribal people in Tamil Nadu.

Cattle-Derived Unsaturated Aldehydes Repel Biting Midges and Mosquitoes

Host-derived repellents offer a novel way to reduce disease vector–host interactions, particularly for vectors and nuisance pests where commercial repellents are not available, e.g., Culicoides biting midges. By revising the criteria previously used to identify bioactive volatile organic compounds for Culicoides nubeculosus, we identify (E)-2-hexenal, (E)-2-heptenal, (E)-2-octenal, and (E)-2-nonenal to be differentially present in the headspace odour of cattle hair and to elicit antennal responses in this research model species. A blend of these unsaturated aldehydes elicited an aversive response in C. nubeculosus, as well as a repellent response in three disease vector mosquito species, Aedes aegypti, Culex quinquefasciatus and Anopheles coluzzii, a response that was stronger than that to the commercially available repellents tested (DEET, IR3535, PMD, icaridin, and d-allethrin). Culicoides nubeculosus was behaviourally indifferent to these commercially available repellents tested, except d-allethrin to which it was attracted. The identification of a host-derived repellent odour blend, which reduces the interaction between biting midges extends the array of tools to be used in integrated vector management of these and other disease vectors.

Novel acylpiperidine analogues as potential aphid repellent agents: Rational design, synthesis and repellent activity

Odorant-binding protein (OBP) is a promising potential target and can be used as a template for developing insect control agents due to its ability to bind to and transport semiochemicals to olfactory receptors, thus triggering behavioural responses among insects. In this study, 27 novel acylpiperidine analogues were designed and synthesised by introducing the hydrophobic long chain of the aphid alarm pheromone (E)-β-farnesene (EβF) into the polar acylpiperidine group of the commercial insect repellent icaridine based on the binding cavity characteristics of an OBP of the pea aphid Acyrthosiphon pisum, ApisOBP3. Compound 14c displayed good repellent activity against the pea aphids with a repellence rate of 61.5% at a concentration of 6 μg/μL. The equilibrium dissociation constant (Ki) of compound 14c against ApisOBP3 was 20.92 μM in competitive fluorescence binding assays; this value is similar to the Ki of the commercial insect repellent icaridine (20.56 μM). Molecular dynamics simulation revealed that the EβF long chain of compound 14c showed considerable hydrophobic interactions with the binding domain of ApisOBP3. Moreover, the acylpiperidine moiety of compound 14c formed one hydrogen bond and multiple carbon–hydrogen bonds with the Phe2 and Asn109 residues, respectively. The binding free energy analysis indicated that the contribution of the van der Waals force to the binding affinity was approximately twice as great as that of the electrostatic force. These studies provide significant guidance for the rational designing and efficient identification of novel insect repellent agents.