Acaricidal activity of Egyptian crude plant extracts against Haemaphysalis longicornis ticks.

Haemaphysalis longicornis is a common Ixodida tick species found in temperate areas of Asian countries. An anti-tick assay was conducted on adult female H. longicornis ticks. Plant extract solutions were prepared at concentrations of 50, 25, and 10 mg/mL. Tick survival and mortality were assessed by counting the number of dead and live ticks at 24 h, 48 h, 72 h, and 96 h posttreatment. Out of 11 plant extracts screened, Artemisia judaica extract exhibited the highest potency with 100% mortality (5/5) at 48 h when applied at high and moderate concentrations (50 and 25 mg/mL). Similar results were observed at 96 h for the 10 mg/mL group compared to the untreated ticks. Cleome droserifolia extract demonstrated partial activity with 60% (3/5) and 20% (1/5) mortality at 96 h posttreatment at concentrations of 50 and 25 mg/mL, respectively. Forsskaolea tenacissima extract showed a weak effect with 100% tick mortality (5/5) only at the highest treatment concentration after 96 h. To confirm the activity of A. judaica, trial 2 was conducted. A. judaica demonstrated potency within 48 h in high dose and 72 h in moderate dose, with 100% mortality (15/15) at 96 h posttreatment compared to untreated ticks. The median lethal time 50 (LT50) values were 30.37 h for the high and 55.08 h for the moderate doses. Liquid chromatography‒mass spectrometry was performed on the most potent candidate (A. judaica) to identify its phytochemical components. The results revealed the presence of 9 compounds identified through manual annotation and 74 compounds from the Global Natural Products Social library. These compounds included terpenoids, steroids, phenylpropanoids, flavonoid glycosides, flavonoids, and benzenoids. Camphor was identified as the major component via both approaches. These findings suggest the potential use of A. judaica extract in the future development of acaricidal therapeutics.

[Analysis of active components of Acorus tatarinowii extracts and its activity against dust mites].

OBJECTIVE: To investigate the activity of Acorus tatarinowii extracts against dust mites, and to isolate and characterize active ingredient of A. tatarinowii extracts. METHODS: The essential oil components were extracted from A. tatarinowii rhizome powder by rotary evaporation with methanol as solvents, followed by petroleum ether extraction and rotary evaporation. The essential oil was mixed with Tween-80 at a ratio of 1:1 and diluted into concentrations of 1.000 00%, 0.500 00%, 0.250 00%, 0.125 00%, 0.062 50% and 0.031 25%, while diluted Tween-80 served as controls. A. tatarinowii essential oil at each concentration (200 µL) was transferred evenly to filter papers containing 100 adult mites, with each test repeated in triplicate, and controls were assigned for each concentration. Following treatment at 25 °C and 75% relative humidity for 24 h, the mean corrected mortality of mites was calculated. The essential oil components were separated by silica gel column chromatography, and the essential oil was prepared in the positive column of medium pressure; and then, each component was collected. Silica gel column chromatography was run with the mobile phase that consisted of petroleum ether solution containing 10% ethyl acetate and pure ethyl acetate, detection wavelength of 254 nm, positive silica gel column as the chromatography column, and room temperature as the column temperature. Each component of the purified A. tatarinowii essential oil was diluted into 1.000 00% for acaricidal tests. The components with less than 100% acaricidal activity were discarded, and the remaining components were diluted into 50% of the previous-round tests for subsequent acaricidal tests. The components with acaricidal activity were subjected to high-performance liquid chromatography, liquid chromatography-mass spectrometry and pulsed-Fourier transform nuclear magnetic resonance spectroscopy. The structure of active monomer compounds was determined by standard spectral library retrieval and literature review. RESULTS: A. tatarinowii essential oil at concentrations of 1.000 00%, 0.500 00%, 0.250 00% and 0.125 00% killed all dust mites, and the corrected mortality was all 100%. Exposure to A. tatarinowii extracts at an effective concentration of 0.062 50% for 24 hours resulted in 94.33% mortality of dust mites. Six components (A to F) were separated using gel column chromatography, and components D and E both showed a 100% acaricidal activity against dust mites at a concentration of 0.50000%. In addition, Component D was identified as isoeugenol methyl ether, and Component E as ß-asarinol. CONCLUSIONS: The extract of A. tatarinowii essential oil has acaricidal activity, and the isoeugenol methyl ether shows a remarkable acaricidal activity against dust mites.

Design, Synthesis, and Acaricidal/Insecticidal Activities of New Phenylpyrazole Derivatives Comprising an Imide Moiety.

Using nicofluprole as the lead compound, we designed and synthesized a series of new phenylpyrazole analogues through substituting the methyl group on the nitrogen atom of the amide with an acyl group. Bioassay results showed that compounds A12-A17 with a 1-cyanocyclopropimide group exhibited outstanding insecticidal activity. The LC50 values for compounds A12-A17 against Tetranychus cinnabarinus ranged from 0.58 to 0.91 mg/L. Compound A15 showed an LC50 value of 0.29 and 3.10 mg/L against Plutella xylostella and Myzus persicae, respectively. Molecular docking indicated the potential binding interactions of compound A15 with a gamma-aminobutyric acid receptor. Additionally, density functional theory calculations implied that the 1-cyanocyclopropimide structure might be essential for its biological activity. Phenylpyrazole derivatives, containing a 1-cyanocyclopropimide fragment, have the potential for further development as potential insecticides.

Attractant and repellent properties of Senna didymobotrya plant extracts to Amblyomma variegatum and Rhipicephalus appendiculatus.

The growing challenge of acaricide resistance and geographical range expansion of invasive tick species demands other interventions, like plant-based alternatives, for sustainable tick control. Leaves, flowers, seedpods, and twig branch extracts of Senna didymobotrya were analyzed using coupled gas chromatography mass spectrometry (GC-MS). Response of adult Amblyomma variegatum and Rhipicephalus appendiculatus to extracts was evaluated. The most attractive plant extract was fractionated and ticks' responses to its fractions assessed. Potential tick attractants in the attractive plant part extract and its fractions were identified by GC-MS analysis. Non- significant qualitative and quantitative differences were observed in the plant parts' extract composition (R = 0.6178). Flower extracts attracted both species, with a 0.1-fold higher attraction in A. variegatum compared to the standard attraction aggregation attachment pheromone (AAAP). Leaf and seedpod extracts repelled ticks at various concentrations. Bioassays after fractionating flower extracts identified hexane and ethyl acetate fractions as most attractive to A. variegatum (P < 0.001) and R. appendiculatus (P < 0.001), respectively. Chemical analysis of the most attractive extracts and fractions identified compounds, including documented acarine attractants, squalene and linoleic acid. A squalene and linoleic acid blend (1:1) at 1 mg/mL significantly attracted adult A. variegatum (P < 0.01) and R. appendiculatus (P < 0.001). The results of this study broaden comprehension of how ticks respond to plants in nature, and showcase the promising potential for integrating these insights into effective tick management programs.

Homologous Design and Three-Dimensional Quantitative Structure-Activity Relationship Study of Acaricidal 2,4-Diphenyloxazolines Containing Different Heteroatoms and Alkyl Chains.

In order to speculate the three-dimensional structure of the potential binding pocket of the chitin synthase inhibitor, a series of 2,4-diphenyloxazoline derivatives with different lengths of alkyl chains and heteroatoms were designed and synthesized by a homologous strategy. The bioassay results indicate that both the length of the alkyl chains and the type of substituents can affect the acaricidal activity against mite eggs. Compounds containing chloropropyl, alkoxyalkyl, and para-substituted phenoxyalkyl or phenylthioalkyl groups exhibit good activity, while those containing steric hindrance substituents or carbonyl substituents on the benzene ring exhibit reduced activity. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study showed that there may be a narrow hydrophobic region deep in the pocket, and the steric effect plays a more important role than the electrostatic effect. The current work will provide assistance for future molecular design and target binding research.

Chemical Composition and Acaricidal Activity of Essential Oil of Lavandula dentata L. on Engorged Females of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

PURPOSE: Rhipicephalus (Boophilus) microplus is one the most significant ectoparasite in cattle farming in tropical and subtropical regions, causing problems to livestock health worldwide. The control of this ectoparasite primarily relies on the use of synthetic acaricides. However, the emergence of acaricide resistance has stimulated the search for new control alternatives, including phytocompounds with acaricidal and insecticidal potential. The aim of this study was to evaluate the acaricidal potential of Lavandula dentata essential oil against the engorged females of R. (B.) microplus. METHODS: Engorged females were obtained from infested bovines in dairy farms in Pernambuco, Brazil. L. dentata essential oil was extracted, and adult immersion test assays were performed using the following oil concentrations: 0.2%, 0.4%, 0.6%, 0.8%, and 1%. RESULTS: L. dentata essential oil at a concentration of 1% was lethal to all engorged females, and concentrations of 0.6% and 0.8% caused mortality of 98.6% and 99.1%, respectively. These concentrations disrupted the reproductive capacity of engorged females, reducing oviposition by more than 90% and preventing egg hatching by over 87%. CONCLUSION: The data revealed that L. dentata essential oil possesses effective pharmacological properties against R. (B.) microplus and could be used for tick control following in vivo evaluation, thus contributing to mitigating the negative impacts of synthetic acaricide use.

Discovery of Pesticide Candidates from Natural Plant Products: Semisynthesis and Characterization of Andrographolide-Based Esters and Study of Their Pesticidal Properties and Toxicology.

To explore the use of nonfood plant-derived secondary metabolites for plant protection, a series of ester derivatives for controlling the major migratory agricultural pests were obtained by structural modification of andrographolide, a labdane diterpenoid isolated from Andrographis paniculata. Compound Id showed good insecticidal activity against the fall armyworm Spodoptera frugiperda Smith. Compounds IIa (LC50: 0.382 mg/mL) and IIIc (LC50: 0.563 mg/mL), the acaricidal activities of which were, respectively, 13.1 and 8.9 times that of andrographolide (LC50: 4.996 mg/mL), exhibited strong acaricidal and control effects against Tetranychus cinnabarinus Boisduval. Against Aphis citricola Van der Goot, compounds IIIc and IVb displayed 3.9- and 3.7-fold pronounced aphicidal activity of andrographolide. Effects of compound Id on three protective enzymes (superoxide dismutase, peroxidase, and catalase) of S. frugiperda were also observed. The obvious differences of epidermal cuticle structures of mites treated with compound IIa were determined by scanning electron microscopy. Structure-activity relationships indicated that 14-ester derivatives of andrographolide showed potential insecticidal/acaricidal activities and can be further utilized as lead compounds.

Construction and Single-Crystal Structures of N-Isoxazolin-5-ylcarbonylindole Derivatives, and Their Pesticidal Activities and Toxicology Study.

To explore natural product-based pesticide candidates, a series of indole derivatives containing the isoxazoline skeleton at the N-1 position were synthesized by 1,3-dipolar [2 + 3] cycloaddition reaction. Their structures were characterized by melting points (mp), infrared (IR) spectra, proton nuclear magnetic resonance spectra (1H NMR), carbon-13 nuclear magnetic resonance spectra (13C NMR), and high resolution mass spectrometry (HRMS). The single-crystal structures of five compounds were presented. Against Tetranychus cinnabarinus Boisduval, compound 3b showed greater than 3.8-fold acaricidal activity of indole and good control effects under glasshouse conditions. Against Aphis citricola Van der Goot, compounds 3b and 3q exhibited 48.3- and 36.8-fold aphicidal activity of indole and 6-methylindole, respectively. Particularly, compound 3b showed good bioactivities against T. cinnabarinus and A. citricola. Against Eriosoma lanigerum Hausmann, compound 3h and 3i showed 2.1 and 1.9 times higher aphicidal activity compared to indole. Furthermore, the construction of the epidermal cuticle layer of 3b-treated carmine spider mites was distinctly damaged, which ultimately led to their death.

In vitro acaricidal activity of essential oils and their binary mixtures against ixodes scapularis (Acari: Ixodidae).

Ixodes scapularis ticks are vectors of infectious agents that cause illness in humans, including Lyme disease. Recent years have seen a surge in tick-borne diseases (TBD) resulting in a high demand for tick management products. Plants offer a valuable source of active compounds for the development of novel, eco-friendly tick control products, reducing potential risks to human and animal health. Essential oils (EOs) have emerged as potential acaricides and repellents against ticks providing an alternative to synthetic chemicals and aiding in the prevention of TBD by lowering the risk of tick bites. We investigated the acaricidal activity of EOs from lemongrass (Cymbopogon citratus), geranium (Pelargonium x asperum), savory thyme (Thymus saturejoides), and white thyme (Thymus zygis) on I. scapularis. The interactions (i.e., synergistic, antagonistic, or additive) of their binary mixtures were also evaluated. EO samples were analyzed via gas chromatography-mass spectrometry to determine their chemical composition. The adult immersion test was used to determine the lethal concentration (LC50) of each EO alone and in mixtures. Quantitative assessment of synergistic, additive, or antagonistic effect of the binary mixtures was performed by calculating the combination index. Strong acaricidal activity was recorded for savory thyme and white thyme EOs, with LC50 values of 28.0 and 11.0 µg/µL, respectively. The LC50 of lemongrass and geranium EOs were 49.0 and 39.7 µg/µL, respectively. Among the tested EOs, savory thyme and white thyme had a strong acaricidal effect on I. scapularis, which might be linked to the presence of carvacrol (26.05 % ± 0.38) and thymol (53.6 % ± 2.31), main components present in savory thyme and white thyme EOs, respectively. The tick killing efficacy of lemongrass and geranium EOs was lower when mixed than when used separately (LC50 of 65.3 µg/µL). The same happened with savory thyme and white thyme EOs, except at 9.75 µg/µL where they had a synergistic effect (LC50 of 58.3 µg/µL). Lemongrass and savory thyme EOs had a synergistic effect at low concentrations, and an antagonistic effect at higher concentrations (LC50 of 95.4 µg/µL). Lemongrass and white thyme EOs had a synergistic effect against ticks from 15 to 120 µg/µL (LC50 of 18.5 µg/µL) similar to white thyme EO. Geranium and savory thyme EOs had an antagonistic effect at all concentrations, with an LC50 of 66.8 µg/µL. Geranium and white thyme EOs also had an antagonistic effect, except at 12.7 µg/µL where they had a synergistic effect (LC50 of 66.8 µg/µL). The interaction observed when combining selected essential oils suggests promising potential for developing acaricidal formulations aimed at controlling ticks and curbing the transmission of tick-borne disease agents.

Optimization of Osthole as a Pesticide Candidate: Synthesis, Crystal Structures, and Agrochemical Properties of Acrylate Derivatives of Isopropenyl 2,3-Dihydrobenzofurans.

For high-value-added application of osthole derivatives as a pesticide candidate in crop protection, by the use of osthole as a lead compound, a series of novel acrylate derivatives of isopropenyl 2,3-dihydrobenzofurans were prepared by the successive bromination, rearrangement, and esterization reactions. Three-dimensional structures of four compounds were determined by single-crystal X-ray diffraction. The possible mechanism for construction of this new isopropenyl 2,3-dihydrobenzofuran skeleton from the osthole was presented. Against Plutella xylostella Linnaeus, compound 32 (R = PhCH2CH2) displayed 3.5-fold potent insecticidal activity of osthole. Against Tetranychus cinnabarinus Boisduval, compound 40 (LC50: 0.165 mg/mL; R = (CH2)13CH3) showed 8.3-fold pronounced acaricidal activity of osthole (LC50: 1.367 mg/mL); notably, its control effect can be comparable to that of the commercial acaricide spirodiclofen. Additionally, the scanning electron microscopy imaging method demonstrated that compound 40 can destroy the stratum corneum of T. cinnabarinus. Compound 40 can be further explored as a lead acaricidal agent.

Novel acaricidal and growth-regulating activity of Aloe vera and Rheum rhabarbarum extracts and their oil/water nanoemulsions against the camel tick, Hyalomma dromedarii.

Hyalomma dromedarii is an important tick species infesting livestock. This work evaluated the novel adulticidal, insect growth-regulating, and enzymatic efficacy of ethanol plant extracts of Aloe vera and Rheum rhabarbarum and their nanoemulsions against males and engorged females of the camel tick, H. dromedarii. The physicochemical properties of nanoemulsions were evaluated. The High-Performance Liquid Chromatography (HPLC) analyses indicated that the extracts contained polyphenols and flavonoids, which could enhance their acaricidal effect. Dynamic light scattering (DLS) of the nanoemulsions of A. vera and R. rhabarbarum were 196.7 and 291 nm, whereas their zeta potentials were - 29.1 and - 53.1 mV, respectively. Transmission electron microscope (TEM) indicated that nanoemulsions showed a regular spherical shape (less than 100 nm). Fifteen days post-treatment (PT) with 25%, the mortality% of A. vera and R. rhabarbarum were 88.5 and 96.2%, respectively. Five days PT, the median lethal concentration values of A. vera, R. rhabarbarum, and their nanoemulsions were 7.8, 7.1, 2.8, and 1.02%, respectively, and their toxicity indices were 91.02, 100, 36.4, and 100%, respectively. Their median lethal time values PT with 3.5% were 6.09, 5.09, 1.75, and 1.34 days, respectively. Nanoemulsions enhanced the efficacy of the crude extract 1-7 folds, 5 days PT, and accelerated their speed of killing ticks 2-4 times. The total protein and carbohydrates, Acetylcholinesterase, Alpha esterase, and Amylase were affected PT. The reproductive potential of engorged females was adversely impacted. In conclusion, the novel A. vera and R. rhabarbarum extracts were promising acaricides, and their nanoformulations enhanced their efficacies.

Integrating In Vitro and In Silico Approaches to Assess Monotheca buxifolia Plant Extract against Rhipicephalus (Boophilus) microplus and Sarcoptes scabiei.

Tick and mite infestations pose significant challenges to animal health, agriculture, and public health worldwide. The search for effective and environmentally friendly acaricidal agents has led researchers to explore natural alternatives. In this study, we investigated the acaricidal potential of the Monotheca buxifolia plant extract against Rhipicephalus microplus ticks and Sarcoptes scabiei mites. Additionally, we employed a computational approach to identify phytochemicals from the extract that could serve as drug candidates against these ectoparasites. The contact bioassay results demonstrated that the M. buxifolia plant extract exhibited significant efficacy against R. microplus and S. scabiei, with higher concentrations outperforming the positive control acaricide permethrin in terms of mite mortality. Time exposure to the extract also showed a positive correlation with better lethal concentration (LC50 and LC90) values. Similarly, the adult immersion test revealed a notable inhibition of tick oviposition via the plant extract, especially at higher concentrations. The two-protein primary structure, secondary structure and stability were predicted using the Expasy's ProtParam server, SOPMA and SUSUI server, respectively. Using Homology modeling, the 3D structure of the protein was obtained and validated through the ERRAT server, and active sites were determined through the CASTp server. The docking analysis revealed that Alpha-Amyrenyl acetate and alpha-Tocopherol exhibited the highest docking scores for S. scabiei and R. microplus aspartic protease proteins, respectively. These phytochemicals demonstrated strong binding interactions, suggesting their potential as acaricidal drug candidates. In conclusion, the M. buxifolia plant extract displayed significant acaricidal activity against R. microplus and S. scabiei. Moreover, the computational approach identified promising phytochemicals that could serve as potential drug candidates for controlling these ectoparasites.

Novel Acaricidal Silico-Containing Pyrazolyl Acrylonitrile Derivatives Identified through Rational Carbon-Silicon Bioisosteric Replacement Strategy.

The identification of novel pyrazolyl acrylonitrile acaricides with improved properties is of great value for the control of phytophagous mites. A series of innovative silicon-containing pyrazolyl acrylonitriles were rationally designed by applying a bioisosteric carbon-silicon replacement strategy and prepared based on novel synthetic methodology. As a result of our research, we discovered compound A25 which possesses outstanding acaricidal activity. With an LC50 value of 0.062 mg/L, compound A25 was found to be 2.3-fold and 1.9-fold more potent than the commercial acaricides cyenopyrafen and cyetpyrafen, respectively. Enzymatic inhibitory assay indicated that the active principle M1 of compound A25 possesses an IC50 value of 2.32 µM against Tetranychus cinnabarinus SDH, which was about twofold superior compared to the active metabolites of cyenopyrafen (IC50 = 4.72 µM). Molecular docking study showed that the active metabolites 2 and 3 and their corresponding silicon counterparts form H-bonds and cation-π interaction with the residues of Trp165, Tyr433, and Arg279.

Combinations of amitraz with essential oils from Lippia sidoides and Thymus vulgaris, thymol and thymol acetate for Rhipicephalus microplus control: studies under laboratory and field conditions.

This study aimed to assess the effect of combining amitraz with essential oils (EOs) from Thymus vulgaris and Lippia sidoides, as well as the monoterpenes thymol and thymol acetate, on Rhipicephalus microplus in laboratory conditions, and to select the most effective combination for testing in field conditions. The chemical analysis showed that EOs were mainly composed of monoterpenes, with thymol and p-cymene as the major compounds. In larval (LIT) and adult (AIT) immersion tests using different concentrations of the oils and terpenes mixed with amitraz, the results showed that both EOs and thymol improved the efficacy of amitraz against larvae and engorged females of R. microplus, whereas thymol acetate only enhanced activity against larvae. The most favorable outcome was obtained with the EO of L. sidoides combined with amitraz, resulting in 99 % and 100 % efficacy against larvae and engorged females, respectively. Furthermore, the combination of amitraz with thymol showed presented an efficacy of 94 % and 91 % against larvae and engorged females, respectively. Thus, for the other tests, the combination of thymol + amitraz was chosen due to the ease of working with pure thymol in bioassays, and easier standardization. The immersion test (thymol + amitraz) with semi-engorged females showed 100 % efficacy for the combination of thymol + amitraz, while in tests with different solvents (thymol + amitraz), ethanol being the most effective solvent among those tested (ethanol, Triton, and Tween), resulting in 95 % efficacy on engorged females. In the field test, in treatments with amitraz and thymol + amitraz, efficacy of 54 % and 74 % was observed on day + 3 and 33 % and 43 % on day + 7, respectively. Assessing the reproductive biology of females recovered from animals treated with amitraz or amitraz + thymol, in day + 7, efficacies of 33 % and 52 %, respectively, were observed. EOs from T. vulgaris and L. sidoides and thymol improved the acaricidal activity of amitraz on larvae and engorged females of R. microplus under laboratory conditions, while thymol acetate only enhanced activity against larvae. Thymol increased the efficacy of amitraz under field conditions, however for the development of a commercially available acaricide to R. microplus control, additional studies are needed to increase the efficacy. Further research is needed (by changing concentrations, adding other compounds and/or developing formulations) to increase acaricidal efficacy and develop new effective products to combat R. microplus infestations in cattle.

Influence of the acaricide emulsion pH on the effectiveness of spray products to control the cattle tick: laboratory and field investigations.

The current work evaluated the efficacy of 10 commercial acaricides in different pHs (4.5, 5.5, and 6.5) in laboratory (adult immersion tests (AIT), pH evaluation over time) and field assays (tick counts and efficacy). In the AIT (n=70), higher efficacies were obtained when the acaricide emulsion had a more acidic pH (4.5), mainly for two combinations of pyrethroids + organophosphate (acaricide 3 and acaricide 9). For amidine, a higher pH (6.5) showed a higher efficacy. Over time, there was a trend in the pH of these emulsions increasing. When the efficacy of chlorpyrifos + cypermethrin + piperonyl butoxide (acaricide 3) at different pHs was evaluated over time (0, 6, 12, and 24h) by AIT, the less acidic pH (6.5) showed a strongly variation in the acaricide efficacy range. The mean pH of the water samples from different regions of Brazil was 6.5. In the field, the association of pyrethroid + organophosphates (acaricide 9) with pH of 4.5 and 5.5 were more effective in tick control than the emulsion prepared with this same spray formulation at pH 6.5. The pH of the acaricide emulsions is an important point of attention and is recommended that the veterinary industry start to develop/share information regarding how the pH can affect the acaricide efficacy.

Expedient discovery of novel oxime ester derivatives of piperine/piperine analogs as potent pesticide candidates and their mode of action against Tetranychus cinnabarinus Boisduval.

BACKGROUND: Nowadays, pest infestation and resistance have appeared as a consequence of repeated and extensive use of pesticides. Thus, development of new effective pesticide candidates in crop protection is highly desirable. Herein, a series of new piperine derivatives containing oxime ester scaffolds were regioselectively and stereoselectively prepared as pesticidal agents. RESULTS: Steric configurations of compounds 2, 5z and 13e were definitively determined by single-crystal X-ray diffraction. Against Tetranychus cinnabarinus, notably, compounds 5f [median lethal concentration (LC50 ) = 0.14 mg mL-1 ] and 5v (LC50 = 0.13 mg mL-1 ) showed >107-fold greater acaricidal activity than piperine (LC50 = 15.02 mg mL-1 ), which were comparable to the commercial acaricide spirodiclofen. Against Aphis citricola, compound 5d (LD50 = 19.12 ng aphid-1 ) exhibited 6.1-fold more potent aphicidal activity than piperine (LD50 = 116.06 ng aphid-1 ). Additionally, through scanning electron microscopy, the toxicology study suggested that the acaricidal activity of piperine derivatives may be related to damage of the cuticle layer crest of T. cinnabarinus. CONCLUSION: The structure-activity relationships suggested that 3,4-dioxymethylene of piperine was crucial for its acaricidal activity; and introduction of a certain length of aliphatic chain at the C-2 position was beneficial to the aphicidal and acaricidal activities. Compounds 5f and 5v are potential leads for further structural modification as acaricidal agents. © 2023 Society of Chemical Industry.

Design and Synthesis of Scopoletin Sulfonate Derivatives as Potential Insecticidal Agents.

(1) Background: Scopoletin and scoparone, two naturally occurring coumarins, have garnered considerable attention and have been introduced to the market in China due to their high insecticidal efficacy and low toxicity. To investigate the structure-activity relationship of these coumarins, a series of scopoletin derivatives with aryl sulfate at C7 and different substitutes at C3 were designed and synthesized, and their insecticidal activity was studied. (2) Methods: A total of 28 new scopoletin derivatives were designed and synthesized. Most target compounds exhibited moderate insecticidal activity against the phytophagous mite Tetranychus cinnabarinus and the brine shrimp Artemia salina. (3) Results: Among these compounds, compounds 5a and 5j possessed the best insecticidal activities against T. cinnabarinus, with LC50 values of 57.0 and 20.0 µg/mL, respectively, whereas that of the control drug was 15.0 µg/mL. Compound 4j exhibited selective insecticidal activities against A. salina, with an LC50 value of 9.36 µg/mL, whereas its LC50 value against T. cinnabarinus was 93.0 µg/mL. The enzymatic inhibitory activity on acetylcholinesterase (AChE) showed a consistent tendency with the insecticidal activity. Further molecular docking analyses predicted the binding conformations of these compounds, which showed a good correlation between the insecticidal activity and the binding scores. (4) Conclusions: In general, a decreased electron cloud density of the Δ3,4 olefinic bond is beneficial for improving the insecticidal activity against both T. cinnabarinus and A. salina. In addition, naphthyl or benzene groups with a sulfate ester at the C7 position could further improve the insecticidal activity against A. salina. AChE was implied to be a site of action for potential insecticidal activity. The results provide insight into the rational design of a new generation of effective coumarin insecticides.

A new ß-class milbemycin derivative from a mutant of genetically engineered strain Streptomyces avermitilis AVE-H39.

A new ß-class milbemycin, 13α-hydroxy milbemycin ß6 (1), was isolated from the fermentation broth of a mutant of genetically engineered strain Streptomyces avermitilis AVE-H39. Its structure and absolute configuration were elucidated by extensive spectroscopic methods and confirmed by single crystal X-ray diffraction.

A novel spiro-heterocycle milbemycin metabolite from a genetically engineered strain of Streptomyces bingchenggensis.

Milbemycin R, a novel spiro-heterocycle milbemycin, was obtained from the metabolites produced by the mutant strain S. bingchenggensis BCJ60B11. Its structure was determined by spectroscopic and spectrometric analyses including 1 D, 2 D NMR, IR, HR-ESI-MS data. The acaricidal and nematicidal activities of milbemycin R against Tetranychus cinnabarinus and Bursaphelenchus xylophilus were tested. Milbemycin R possessed better acaricidal activity than milbemycins A3/A4.

Molecular characterization of Hyalomma dromedarii and evaluation of acaricidal potential of herbal methanolic extracts against H. dromedarii larvae in comparison to synthetic acaricides.

The present study had two aims: molecular characterization of Hyalomma dromedarii infesting one-humped camels of Haryana (North India), and assessment of the acaricidal potential of herbal methanolic extracts against H. dromedarii larvae in comparison to synthetic acaricides. Phylogenetics and population neutrality indices were assessed by targeting partial amplification of mitochondrial 16S rDNA sequences. Larval packet test (LPT) was performed to evaluate the acaricidal efficacy of herbal extracts (Ferula asafoetida and Trachyspermum ammi) and synthetic acaricides (deltamethrin and fipronil). Phylogenetic studies established the collected ticks to be H. dromedarii, exhibiting a homology of 99.8-100%. However, the present study isolates formed a different sub-clade compared to H. dromedarii sequences from Egypt, Senegal, Tunisia and Saudi Arabia. Nucleotide and haplotype diversity values were indicative of demographic expansion and low gene flow. Negative values of Tajima's D (-0.612) and Fu and Li's Fst (-0.479) highlighted deviations from neutrality and emphasized recent population expansion. The median lethal concentration (LC50) values recorded for T. ammi, F. asafoetida and their combination were 3.68, 2.87 and 2.59 mg/mL, respectively, whereas the 90% lethal concentration (LC90) values were 4.09, 3.58 and 3.35 mg/mL, respectively. It was also observed that the H. dromedarii population under study was completely susceptible to both the formulated synthetic acaricides. In conclusion, combination of methanolic extracts of F. asafoetida and T. ammi could provide a potential substitute to toxic synthetic chemical acaricides and might prove a valuable component of integrated tick management strategies.