A new Bowman-Birk type protease inhibitor regulated by MeJA pathway in maize exhibits anti-feedant activity against the Ostrinia furnacalis.

Jasmonic acid (JA), an important plant hormone, plays a crucial role in defending against herbivorous insects. In this study, we have identified a new Bowman-Birk type protease inhibitor (BBTI) protein in maize that is regulated by the JA pathway and exhibits significant antifeedant activity, which is notably induced by exogenous Methyl Jasmonate and Ostrinia furnacalis feeding treatments. Bioinformatics analysis revealed significant differences in the BBTI protein among different maize inbred lines, except for the conserved domain. Prokaryotic and eukaryotic expression systems were constructed and expressed, and combined with bioassays, it was demonstrated that the antifeedant activity of BBTI is determined by protein modifications and conserved domains. Through RT-qPCR detection of BBTI and JA regulatory pathway-related genes' temporal expression in different maize inbred lines, we identified the regulatory mechanism of BBTI synthesis under the JA pathway. This study successfully cloned and identified the MeJA-induced anti-feedant activity gene BBTI and conducted functional validation in different maize inbred lines, providing valuable insights into the response mechanism of insect resistance induced by the plant JA pathway. The increased expression of the anti-feedant activity gene BBTI through exogenous MeJA induction may offer a potential new strategy for mediating plant defense against Lepidoptan insects.

Trichoplusia ni Transcriptomic Responses to the Phytosaponin Aglycone Hederagenin: Sex-Related Differences.

Many plant species, particularly legumes, protect themselves with saponins. Previously, a correlation was observed between levels of oleanolic acid-derived saponins, such as hederagenin-derived compounds, in the legume Medicago truncatula and caterpillar deterrence. Using concentrations that reflect the foliar levels of hederagenin-type saponins, the sapogenin hederagenin was not toxic to 4th instar caterpillars of the cabbage looper Trichoplusia ni nor did it act as a feeding deterrent. Female caterpillars consumed more diet than males, presumably to obtain the additional nutrients required for oogenesis, and are, thus, exposed to higher hederagenin levels. When fed the hederagenin diet, male caterpillars expressed genes encoding trypsin-like proteins (LOC113500509, LOC113501951, LOC113501953, LOC113501966, LOC113501965, LOC113499659, LOC113501950, LOC113501948, LOC113501957, LOC113501962, LOC113497819, LOC113501946, LOC113503910) as well as stress-responsive (LOC113503484, LOC113505107) proteins and cytochrome P450 6B2-like (LOC113493761) at higher levels than females. In comparison, female caterpillars expressed higher levels of cytochrome P450 6B7-like (LOC113492289). Bioinformatic tools predict that cytochrome P450s could catalyze the oxygenation of hederagenin which would increase the hydrophilicity of the compound. Expression of a Major Facilitator Subfamily (MFS) transporter (LOC113492899) showed a hederagenin dose-dependent increase in gene expression suggesting that this transporter may be involved in sapogenin efflux. These sex-related differences in feeding and detoxification should be taken into consideration in insecticide evaluations to minimize pesticide resistance.

The effect of Xenorhabdus bacteria metabolites on Colorado potato beetle (Leptinotarsa decemlineata) adult feeding and larval survival.

Colorado Potato Beetle (CPB) is one of the most destructive potato pests that can quickly develop resistance to insecticides. Therefore, new safe and effective control strategies that are less susceptible to the development of resistance by CPB are urgently needed. Due to their complex mode of action, the likelihood of resistance development by target pests is generally low with antifeedants. In the present study, we assessed the effect of secondary metabolites of various Xenorhabdus bacteria species and strains on CPB adult feeding and on larval development. The metabolites were applied in the form of cell free supernatants (CFSs) from Xenorhabdus cultures. In bioassay 1, leaves treated with ten Xenorhabdus cultures were fed to CPB adults, and their feeding was assessed daily for one week. In bioassay 2, CPB egg masses were placed on the leaves treated with five bacterial cultures, and larval development to pupae was monitored. Out of the ten Xenorhabdus cultures tested, two strains exhibited a significant reduction in the feeding behavior of Colorado Potato Beetle adults, with reductions of up to 70% compared to the control. The effect of CFSs on larval development was variable, and when treated with X. khoisanae SGI 197, over 90% of larvae died in the first few days before reaching the 2nd instar, and complete mortality was achieved on the 8th day of the experiment. Our study is the first study to demonstrate the antifeedant effect of Xenorhabdus cultures towards herbivorous beetles, and the metabolites of these bacteria may have potential for CPB control. Clearly, the metabolites produced by X. khoisanae SGI-197 may be a promising tool for CPB larvae control with the potential to significantly decrease damage to potato plants.

Insecticidal, antifeedant and acetylcholinesterase inhibitory activity of sesquiterpenoids derived from eudesmane, their molecular docking and QSAR.

This work evaluated the insecticidal, antifeedant and AChE inhibitory activity of compounds with eudesmane skeleton. The insecticidal activity was tested against larvae of Drosophila melanogaster and Cydia pomonella, the compounds 3 and 4 were the most active (LC50 of 104.2 and 106.7 µM; 82.0 and 84.4 µM, respectively). Likewise, the mentioned compounds were those that showed the highest acetylcholinesterase inhibitory activity, with IC50 of 0.26 ± 0.016 and 0.77 ± 0.016 µM, respectively. Enzyme kinetic studies, as well as molecular docking, show that the compounds would be non-competitive inhibitors of the enzyme. The antifeedant activity on Plodia interpunctella larvae showed an antifeedant index (AI) of 99% at 72 h for compounds 16, 27 and 20. The QSAR studies show that the properties associated with the polarity of the compounds would be responsible for the biological activities found.

New Antifungal and Antifeedant Metabolites from Daldinia Eschscholtzii Cocultured with Colletotrichum Pseudomajus.

The synchronous co-culture of Daldinia eschscholtzii and Colletotrichum pseudomajus produced one new linear polyketide, eschscholin C (1), along with three known compounds (2-4). One new acorane sesquiterpene, coldaldrin A (5), and one new amide derivative, coldaldamide A (6) as the probe for polyketide intermediate capture, and three known compounds (7-9) were isolated from the sequential co-culture of D. eschscholtzii with C. pseudomajus. The structures and absolute configurations of 1, 5 and 6 were established by spectroscopic analysis including 1D, 2D NMR, the calculations of the NMR, and ECD data. Most compounds showed significant antifungal activities against the tea pathogens C. pseudomajus, and Fusarium asiaticum with MICs of 2-8 µg/mL. Compound 4 also showed antifeedant activity against silkworms with feeding deterrence indices of 79 % at the concentration of 50 µg/cm2.

Four New Furofuran Lignans from Phryma leptostachya Inhibit the Accumulation of Molting Hormones in Armyworm.

Furofuran lignans have been identified as the main substances responsible for the biological activities of the plant genus Phryma. Here, four new phrymarolin-type leptolignans A-D (7-10) and eight previously known lignans were isolated from P. leptostachya. Of these, nine exhibited significant antifeedant activity against armyworm (Mythimna separata) through a dual-choice bioassay, with the EC50 values ranging from 0.58 to 10.08 µg/cm2. In particular, the newly identified lignan leptolignan A (7) showed strong antifeedant activity, with an EC50 value of 0.58 ± 0.34 µg/cm2. Further investigation found that leptolignan A can inhibit the growth and nutritional indicators in the armyworm M. separata. The concentrations of two molting hormones, 20-hydroxyecdysone and ecdysone, were also found to decrease significantly following the treatment of the armyworms with the lignan, implying that the target of the P. leptostachya lignan may be involved in 20-hydroxyecdysone and ecdysone synthesis. These results enrich our knowledge of P. leptostachya metabolite structural diversity, and provide a theoretical basis for the control of armyworm using lignans.

Recent Advances in Grayanane Diterpenes: Isolation, Structural Diversity, and Bioactivities from Ericaceae Family (2018-2024).

Diterpenes represent one of the most diverse and structurally complex families of natural products. Among the myriad of diterpenoids, grayanane diterpenes are particularly notable. These terpenes are characterized by their unique 5/7/6/5 tetracyclic system and are exclusive to the Ericaceae family of plants. Renowned for their complex structures and broad spectrum of bioactivities, grayanane diterpenes have become a primary focus in extensive phytochemical and pharmacological research. Recent studies, spanning from 2018 to January 2024, have reported a series of new grayanane diterpenes with unprecedented carbon skeletons. These compounds exhibit various biological properties, including analgesic, antifeedant, anti-inflammatory, and inhibition of protein tyrosine phosphatase 1B (PTP1B). This paper delves into the discovery of 193 newly identified grayanoids, representing 15 distinct carbon skeletons within the Ericaceae family. The study of grayanane diterpenes is not only a deep dive into the complexities of natural product chemistry but also an investigation into potential therapeutic applications. Their unique structures and diverse biological actions make them promising candidates for drug discovery and medicinal applications. The review encompasses their occurrence, distribution, structural features, and biological activities, providing invaluable insights for future pharmacological explorations and research.

Synergism and toxicity of iron nanoparticles derived from Trigonella foenum-graecum against pyrethriod treatment in S. litura and H. armigera (Lepidoptera: Noctuidae).

The tobacco cutworm, Spodoptera litura and cotton bollworm, Helicoverpa armigera (Lepidoptera: Noctuidae) are important pests of various agricultural crops that cause sevier economic loses throughout the world. Indiscriminate and frequent use of insecticide may lead to development of resistance in these pests. Nanotechnology has given an alternative to manage and overcome insecticide resistance for pest management strategies. In the present study the iron nanoparticles derived from Trigonella foenum-graecum leaf extract (FeNPs) was investigated for its ecofriendly management of pyrethroid resistance in two lepidopteron pest species at 24 h, 48 h and 72 h post treatment. The result showed high mortality (92.83% and 91.41%) of S. litura and H. armigera at 72 h treatment upon FeNPs and fenvalerate (Fen + FeNPs) teratment. Probit analysis revealed high LC50 upon Fen + FeNPs treatment (130.31 and 89.32 mg/L) with a synergism ratio of 1.38 and 1.36. Antifeedant activity of six dofferent concentration of FeNPs revelaed increased antifeedant activity with respect to increasing concentration of nanoparticles ranging from 10 to 90% and 20-95% againt both insects (p<0.05). Detoxification activity of carboxylesterase was elevated at 630 µmol/mg protein/min (p<0.05) in fenvalerate treatment, whereas decreased activity was found (392umole/mg protein/min) in FeNPs and Fen + FeNPs treatment (P<0.001). GST and P450 activity was also increased in fenvalerate treatment, whereas decreased activity was observed in FeNPs and Fen + FeNPs. Esterase isoenzyme banding pattern revealed four bands in fenvalerate treatment and two bans (E3 and E4) in Fen + FeNPs combination. Hence the present study concludes that T. foenum-graecum synthesized iron nanoparticles could be an effective alternate for ecofriendly management of S. litura and H. armigera.

Genome Mining and Molecular Networking Guided Isolation of Antimycin Analogs with Antifeedant Activities from the Deep-Sea-Derived Streptomyces sp. NA13.

Polyphagous insects could affect agricultural production, which leads to serious economic losses. Due to the negative effects of synthesized insecticides, finding eco-friendly and new biopesticides is emergent. To develop natural origin insecticides, an integrative approach combining antifeedant activity screening, genome mining, and molecular networking has been applied to discover antifeedant secondary metabolites from Streptomyces sp. NA13, which leads to the isolation of a novel antimycin Q (1) and six known antimycin analogs (antimycins A1a, A2a, A3a, A4a, A7a, and N-formylantimycic acid methyl ester, 2-7). Their structures were identified by high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopic. The absolute configuration of 1 was elucidated by the comparison of coupling constant, electronic circular dichroism (ECD) analysis, and NMR calculations. 1-6 exhibited different levels of antifeedant activities against Helicoverpa armigera, especially 1-4. At the same time, the antifeedant activity of antimycin was reported firstly.

Anti-Mitochondrial and Insecticidal Effects of Artemisinin against Drosophila melanogaster.

Artemisinin (ART) is an endoperoxide molecule derived from the medicinal plant Artemisia annua L. and is clinically used as an antimalarial drug. As a secondary metabolite, the benefit of ART production to the host plant and the possible associated mechanism are not understood. It has previously been reported that Artemisia annua L. extract or ART can inhibit both insect feeding behaviors and growth; however, it is not known whether these effects are independent of each other, i.e., if growth inhibition is a direct outcome of the drug's antifeeding activity. Using the lab model organism Drosophila melanogaster, we demonstrated that ART repels the feeding of larvae. Nevertheless, feeding inhibition was insufficient to explain its toxicity on fly larval growth. We revealed that ART provoked a strong and instant depolarization when applied to isolated mitochondria from Drosophila while exerting little effect on mitochondria isolated from mice tissues. Thus, ART benefits its host plant through two distinct activities on the insect: a feeding-repelling action and a potent anti-mitochondrial action which may underlie its insect inhibitory activities.

Insect Antifeedant Benzofurans from Pericallis Species.

In this work, we have studied the benzofurans of Pericallis echinata (aerial parts and transformed roots), P. steetzii (aerial parts and transformed roots), P. lanata (aerial parts), and P. murrayi (aerial parts and roots). This work has permitted the isolation of the new benzofurans 10-ethoxy-11-hydroxy-10,11-dihydroeuparin (10), (-)-eupachinin A ethyl ether (12), 11,15-didehydro-eupachinin A (13), 10,12-dihydroxy-11-angelyloxy-10,11-dihydroeuparin (14), 2,4-dihydroxy-5-formyl-acetophenone (15) isolated for the first time as a natural product, 11-angelyloxy-10,11-dihydroeuparin (16), and 12-angelyloxyeuparone (17), along with several known ones (1-9, 11). In addition, the incubation of the abundant component, 6-hydroxytremetone (1), with the fungus Mucor plumbeus has been studied. Benzofurans in the tremetone series (1, 1a, 2-5, 18, 18a), the euparin series (6, 7, 7a, 8-10, 14, 16), and the eupachinin-type (11, 12) were tested for antifeedant effects against the insect Spodoptera littoralis. The antifeedant compounds (1, 4, 6, 11, 12) were further tested for postingestive effects on S. littoralis larvae. The most antifeedant compounds were among the tremetone series, with 3-ethoxy-hydroxy-tremetone (4) being the strongest antifeedant. Glucosylation of 1 by its biotransformation with Mucor plumbeus gave inactive products. Among the euparin series, the dihydroxyangelate 14 was the most active, followed by euparin (6). The eupachinin-type compounds (11, 12) were both antifeedants. Compounds 4, 11, and 12 showed antifeedant effects without postingestive toxicity to orally dosed S. littoralis larvae. Euparin (6) had postingestive toxicity that was enhanced by the synergist piperonyl butoxide.

The traditional herb Polygonum hydropiper from China: a comprehensive review on phytochemistry, pharmacological activities and applications.

CONTEXT: Polygonum hydropiper L. (Polygonaceae) (PH) is a traditional Chinese traditional medicine with a pungent flavor and mild drug properties. PH is mainly distributed in the channel tropism in the stomach and large intestine. PH has multiple uses and can be used to treat a variety of diseases for a long time. OBJECTIVE: This review summarizes the phytochemical and pharmacological activities, and applications of PH from 1980 to 2022. We also provide suggestions for promoting further research and developing additional applications of PH. METHODS: The data and information on PH from 1980 to 2022 reviewed in this article were obtained from scientific databases, including Science Direct, PubMed, Science Citation Index, SciFinder Scholar (SciFinder), Springer, American Chemical Society (ACS) Publications, and China National Knowledge Infrastructure (CNKI), etc. Some information was obtained from classic literature on traditional Chinese medicines. The search terms were Polygonum hydropiper, phytochemistry compositions of Polygonum hydropiper, pharmacological activities of Polygonum hydropiper, and applications of Polygonum hydropiper. RESULTS: The comprehensive analysis of the literature resulted in 324 compounds being isolated, identified, and reported from PH. Regarding traditional uses, the majority of phytochemical and pharmacological studies have indicated the diverse bioactivities of PH extracts, flavonoids, and volatile oil elements, including antibacterial, antifungal, insecticidal, antioxidant, and anti-inflammatory. CONCLUSIONS: PH has a long history of diversified medicinal uses, some of which have been verified in modern pharmacological studies. Further detailed studies are required to establish scientific and reasonable quality evaluation standards and action mechanisms of active constituents from PH.

Profile of commercialized aphicides on the survivorship and feeding behavior of the cotton aphid, Aphis gossypii.

The cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is one of the most destructive agricultural pests due to photosynthate removal and horizontal transmission of plant viruses. Horizontal transmission of plant viruses by aphids occurs during distinct feeding behavioral events, such as probing for non-persistent viruses or phloem feeding for persistent viruses. We employed toxicity bioassays and electrical penetration graph (EPG) methodology to compare toxicity and quantify changes to feeding behavior and toxicity of A. gossypii after exposure to commercialized aphicides. Commercialized aphicides containing flupyradifurone, sulfoxaflor, thiamethoxam, thiamethoxam + lambda cyhalothrin, and bifenthrin induced >90% aphid mortality within 4 h of exposure. Flupyradifurone was the most acutely toxic aphicide studied with an LT50 of 8.9 min after exposure, which was approximately 3-fold lower than bifenthrin and thiamethoxam + lambda cyhalothrin. This was supported by our EPG results that showed a significant reduction in the proportion of aphids that continued to probe on cotton 4 h after exposure to flonicamid, thiamethoxam, flupyradifurone, bifenthrin, and thiamethoxam + lambda cyhalothrin. The commercialized aphicides containing spirotetramat, flonicamid, thiamethoxam, flupyradifurone, bifenthrin, sulfoxaflor, and pymetrozine significantly (P < 0.05) decreased the time to first probe when compared to the untreated control. Lastly, E1 (phloem salivation) and E2 (phloem ingestion) waveforms were significantly (P < 0.05) reduced for flupyradifurone, flonicamid, thiamethoxam, sulfoxaflor, and thiamethoxam. These data provide a comparative study for the development of new aphicides aiming to induce acute lethality and reduce aphid transmission of plant viruses.

New Metabolites, Antifeedant, Insecticidal Activities, and Reciprocal Relationship Between Insect and Fungus from Endophyte Schizophyllum commune.

Five new bisabolane sesquiterpenes, a new polyketide, along with seven known compounds, were isolated from endophyte Schizophyllum commune associated with a famous medicinal and edible plant, Gastrodia elata. Most compounds 1-12, and extract indicated antifeedant activities against silkworm with feeding deterrence index (FDI) of 21-85 %, at concentrations of 20 µg/cm2 , 40 µg/cm2 , respectively. Compound 6 indicated obvious insecticidal activity with fatality rate of 60 %, at the concentration of 20 µg/cm2 . Five bisabolane sesquiterpenes, two ergosterols, and a glyceride showed insecticidal synergism by combining with abamectin. Interesting, ergosterol peroxide (13) distributed widely in mushrooms and fungi, was found to have feeding attractant activities on insects and antifungal activity against entomopathogen Beauveria bassiana. The reciprocal relationship should be occurred between S. commune and pests for the fungus produced ergosterol peroxide to attract the pests propagating spore, and its anti-entomopathogen activity was also benefit for the health of insects.

Antifeedant and Antifungal Activities of Metabolites Isolated from the Coculture of Endophytic Fungus Aspergillus tubingensis S1120 with Red Ginseng.

A new globoscinic acid derivative, aspertubin A (1) along with four known compounds, were obtained from the co-culture of Aspergillus tubingensis S1120 with red ginseng. The chemical structures of compounds were characterized by using spectroscopic methods, the calculated and experimental electronic circular dichroism. Panaxytriol (2) from red ginseng, and asperic acid (4) showed significant antifeedant effect with the antifeedant rates of 75 % and 80 % at the concentrations of 50 µg/cm2 . Monomeric carviolin (3) and asperazine (5) displayed weak attractant activity on silkworm. All compounds were assayed for antifungal activities against phytopathogens A. tubingensis, Nigrospora oryzae and Phoma herbarum and the results indicated that autotoxic aspertubin A (1) and panaxytriol (2) possessed selective inhibition against A. tubingensis with MIC values at 8 µg/mL. The co-culture extract showed higher antifeedant and antifungal activities against P. herbarum than those of monoculture of A. tubingensis in ordinary medium. So the medicinal plant and endophyte showed synergistic effect on the plant disease resistance by active compounds from the coculture of A. tubingensis S1120 and red ginseng.

Antifeedant Mechanism of Dodonaea viscosa Saponin A Isolated from the Seeds of Dodonaea viscosa.

Dodonaea viscosa is a medicinal plant which has been used to treat various diseases in humans. However, the anti-insect activity of extracts from D. viscosa has not been evaluated. Here, we found that the total saponins from D. viscosa (TSDV) had strong antifeedant and growth inhibition activities against 4th-instar larvae of Spodoptera litura. The median antifeeding concentration (AFC50) value of TSDV on larvae was 1621.81 µg/mL. TSDV affected the detoxification enzyme system of the larvae and also exerted antifeedant activity possibly through targeting the γ-aminobutyric acid (GABA) system. The AFC50 concentration, the carboxylesterase activity, glutathione S-transferases activity, and cytochrome P450 content increased to 258%, 205%, and 215%, respectively, and likewise the glutamate decarboxylase activity and GABA content to 195% and 230%, respectively, in larvae which fed on TSDV. However, D. viscosa saponin A (DVSA) showed better antifeedant activity and growth inhibition activity in larvae, compared to TSDV. DVSA also exerted their antifeedant activity possibly through targeting the GABA system and subsequently affected the detoxification enzyme system. Further, DVSA directly affected the medial sensillum and the lateral sensillum of the 4th-instar larvae. Stimulation of Spodoptera litura. with DVSA elicited clear, consistent, and robust excitatory responses in a single taste cell.

Some sawfly larvae survive predator-prey interactions with pentatomid Picromerus bidens.

Most Asopinae stinkbugs (Hemiptera: Pentatomidae) prey on other insects, including sawfly larvae (Hymenoptera: Symphyta). Sawfly larvae of the Argidae and Pergidae contain toxic peptides, but whether they are defended against stinkbugs remains poorly studied. A literature survey indicates that no publication is devoted to laboratory tests specifically using these sawflies against stinkbugs. Here, laboratory bioassays were made with the stinkbug Picromerus bidens and four sawfly species at last larval instars: Arge ochropus (Argidae), Arge pagana (also tested at medium instars), Lophyrotoma zonalis (Pergidae), and Allantus rufocinctus (Tenthredinidae). Following 24 h of possible predator-prey interactions, no larvae of A. rufocinctus survived, whereas most or all larvae of the other sawfly species did survive and were still alive 48 h later. When feeding on an argid or pergid larva, the feeding periods lasted on average 6-20 s only, some bugs removing their rostrum and abruptly backing away. Full-grown larvae of A. pagana were attacked less than younger ones. It is likely that the tested Argidae and Pergidae are well defended against P. bidens by potent, internal antifeedants, while defensive body movements combined with a large body size play a secondary role.

Anti-Herbivore Activity of Oregonin, a Diarylheptanoid Found in Leaves and Bark of Red Alder (Alnus rubra).

Plants synthesize a wide range of bioactive secondary metabolites to defend against pests and pathogens. Red alder (Alnus rubra) bark, root, and leaf extract have a long history of use in traditional medicine and hygiene. Diarylheptanoids, especially oregonin ((5S)-1,7-bis(3,4-dihydroxyphenyl)-5-(ß-D-xylopyranosyloxy)-heptan-3-one), have been identified as major bioactive constituents. Diarylheptanoids have become a focus of research following reports of their antioxidant, antifungal, and anti-cancer activities. Recent data suggest that high oregonin concentration is associated with resistance of red alder leaves to western tent caterpillar (Malacosoma californicum) defoliation. Here we test effects of this compound directly on leaf-eating insects. Purified oregonin was examined in insect choice and toxicity tests using lepidopteran caterpillars. The compound exhibited significant anti-feedant activity against cabbage looper (Trichoplusia ni), white-marked tussock moth (Orgyia leucostigma), fall webworm (Hyphantria cunea), and M. californicum at concentrations corresponding to oregonin content of the most resistant alder clones in previous experiments. Toxicity tests were carried out with cabbage looper larvae only, but no contact or ingested toxicity was detected. Our results suggest that oregonin at levels found in red alder leaves early in the growing season may contribute to protecting red alder from leaf-eating insects.

Green catalyst Cu(II)-enzyme-mediated eco-friendly synthesis of 2-pyrimidinamines as potential larvicides against Culex quinquefasciatus mosquito and toxicity investigation against non-target aquatic species.

Novel one-pot multicomponent synthesis of 2-pyrimidinamine derivatives can be achieved via green chemistry, using Cu(II)-tyrosinase enzyme (Cu-Tyr) as a catalyst. This method offers mild reaction conditions and a high yield of derivatives. We synthesised several compounds in this manner and evaluated their larvicidal, and antifeedant activities. Out of the synthesised derivatives, compound 3, with a median lethal dose (LD50) of 21.43 µg/mL, was highly active against Culex quinquefasciatus, compared to compounds 1a-m and 2, and the control, hydantocidin. Compounds 1j, 1d, and 1e were low active against C. quinquefasciatus with LD50 values of 78.46, 78.59, and 79.54 µg/mL, respectively. In antifeedant screening, compounds 1j, 1l, and 2 generated 100% mortality within 24 h against Oreochromis mossambicus at 100 µg/mL, where toxicity was determined as the ratio of the number of dead and live fingerlings (%) at 24 h. In contrast, compounds 1a-f, 1i, 1m, and 3 were less toxic to O. mossambicus as compared to the control, dibromoisophakellin. Therefore, compound 3 had high larvicidal activity against C. quinquefasciatus and was less toxic to non-target aquatic species. Molecular docking studies also supported the finding that compound 3 was an effective larvicide with more inhibition ability than the control hydantocidin (-9.6 vs. -6.1 kcal/mol).

Flupyradifurone reduces nectar consumption and foraging but does not alter honey bee recruitment dancing.

Foraging is essential for honey bee colony fitness and is enhanced by the waggle dance, a recruitment behavior in which bees can communicate food location and quality. We tested if the consumption of nectar (sucrose solution) with a field-realistic concentration of 4 ppm flupyradifurone (FPF) could alter foraging behavior and recruitment dancing in Apis mellifera. Foragers were repelled by FPF. They visited the FPF feeder less often and spent less time imbibing sucrose solution (2.5 M, 65% w/w) with FPF. As a result, bees feeding on the FPF treatment consumed 16% less nectar. However, FPF did not affect dancing: there were no effects on unloading wait time, the number of dance bouts per nest visit, or the number of dance circuits performed per dance bout. FPF could therefore deter bees from foraging on contaminated nectar. However, the willingness of bees to recruit nestmates for nectar with FPF is concerning. Recruitment can rapidly amplify the number of foragers and could overcome the decrease in consumption of FPF-contaminated nectar, resulting in a net inflow of pesticide to the colony. FPF also significantly altered the expression of 116 genes, some of which may be relevant for the olfactory learning deficits induced by FPF and the toxicity of FPF.