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Nicotinic acetylcholine receptor (nAChR) is recognized as a significant insecticide target for neonicotinoids and some agonists. In this study, the nAChR α1 subunit from Apis mellifera was first found to be narrowly tuned to different bee toxicity insecticides, namely, sulfoxaflor (SFX) and flupyradifurone (FPF). Hence, novel sulfoximine derivatives 7a-h were rationally designed and synthesized by introducing a benzo[d][1,3]dioxole moiety into a unique sulfoximine skeleton based on the binding cavity characteristics of Amelα1/ratβ2. The two electrode voltage clamp responses of 7a-h were obviously lower than that of SFX, indicating their potentially low bee toxicity. Besides, representative compounds 7b and 7g exhibited low bee toxicity (LD 50  > 11.0 μg/bee at 48 h) revealed by acute contact toxicity bioassays. Molecular modelling results indicated that Ile152, Ala151, and Val160 from honeybee subunit Amelα1 and Lys144 and Trp80 from aphid subunit Mpα1 may be crucial for bee toxicity and aphicidal activity, respectively. These results clarify the toxic mechanism of agonist insecticides on nontargeted pollinators and reveal novel scaffold sulfoximine aphicidal candidates with low bee toxicity. These results will provide a new perspective on the rational design and highly effective development of novel eco-friendly insecticides based on the structure of the nAChR subunit., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The migratory locust, Locusta migartoria, is a major agricultural insect pest and its resistance to insecticides is becoming more prevalent. Cytochrome P450 monooxygenases (CYPs) are important enzymes for biotransformations of various endogenous and xenobiotic substances. These enzymes play a major role in developing insecticide resistance in many insect species. In this study, we heterologously co-expressed a CYP enzyme (CYP6FD1) and cytochrome P450 reductase (CPR) from L. migartoria in Sf9 insect cells. The recombinant enzymes were assayed for metabolic activity towards six selected model substrates (luciferin-H, luciferin-Me, luciferin-Be, luciferin-PFBE, luciferin-CEE and 7-ethoxycoumarin), and four selected insecticides (deltamethrin, chlorpyrifos, carbaryl and methoprene). Recombinant CYP6FD1 showed activity towards 7-ethoxycoumarin and luciferin-Me, but no detectable activity towards the other luciferin derivatives. Furthermore, the enzyme efficiently oxidized deltamethrin to hydroxydeltamethrin through an aromatic hydroxylation in a time-dependent manner. However, the enzyme did not show any detectable activity towards the other three insecticides. Our results provide direct evidence that CYP6FD1 is capable of metabolizing deltamethrin. This work is a step towards a more complete characterization of the catalytic capabilities of CYP6FD1 and other xenobiotic metabolizing CYP enzymes in L. migratoria., (Copyright © 2019. Published by Elsevier Inc.)

Cytochrome P450 monooxygenases (P450s) play important roles in metabolizing various insecticides and often contribute to the development of insecticide resistance in insects and other arthropod species. The objective of this study was to compare the metabolism of four commonly used pyrethroids including deltamethrin, fluvalinate, fenvalerate, and permethrin in the midgut tissue of Locusta migratoria Linnaeus (Orthoptera: Acrididae) by using synergism bioassay and ultra-performance liquid chromatography (UPLC)-mass spectrometer (MS) analyses. Our study showed that piperonyl butoxide (PBO, P450 enzyme inhibitor) can significantly synergize the toxicity of deltamethrin, fluvalinate, and fenvalerate with synergism ratios ranging from 1.30 to 1.70 folds. Preincubations of the midgut tissue with PBO followed by incubations with each of the four pyrethroids resulted in significantly higher amounts of unmetabolized deltamethrin and fluvalinate than those in the control (preincubation without PBO) as well as preincubations with other two detoxification enzyme inhibitors. These results indicate that P450s play important roles in metabolizing deltamethrin and fluvalinate in the midgut tissue. Our further study using deltamethrin as a representative pyrethroid and UPLC-MS techniques confirmed that the reduced amount of deltamethrin in the control (preincubation without PBO) was due to the metabolism of deltamethrin to yield hydroxydeltamethrin which is a major metabolite produced by P450-mediated aromatic hydroxylation of deltamethrim. These results provide new insights into differential metabolic activity of P450s towards different pyrethroids in the midgut tissue of L. migratoria.

Cytochrome P450s (CYPs) constitute one of the largest gene super families and distribute widely in all living organisms. In this study, the full-length cDNA sequences of two LmCYP9A genes (LmCYP9AQ1 and LmCYP9A3) were cloned from Locusta migratoria. We analyzed the expression patterns of two LmCYP9A genes in various tissues and different developmental stages using real-time quantitative PCR. Then we evaluated the detoxification functions of the two LmCYP9A genes by testing mortalities with four kinds of pyrethroid treatment after RNA interference (RNAi), respectively. Combining with docking structure of two LmCYP9A genes, their detoxification properties were extensively analyzed. The full-length cDNAs of LmCYP9AQ1 and LmCYP9A3 putatively encoded 525 and 524 amino acid residues, respectively. Both LmCYP9A genes were expressed throughout the developmental stages. The expression of LmCYP9AQ1 in the brain was higher than that in other examined tissues, whereas the LmCYP9A3 was mainly expressed in the fat body. The mortalities of nymphs exposed to deltamethrin and permethrin increased from 27.7% to 77.7% and 27.7% to 58.3%, respectively, after dsLmCYP9A3 injection. While the mortalities of nymphs exposed to fluvalinate increased from 29.8% to 53.0% after LmCYP9AQ1 was silenced using RNA interference. Our results suggested that the two LmCYP9A genes may be involved in different pyrethroid insecticide detoxification in L. migratoria., (Copyright © 2016 Elsevier B.V. All rights reserved.)

ABSTRACT As an egg parasitoid, Trichogramma ostriniae (T. ostriniae) exhibits a broad host range and plays a crucial role in controlling various lepidopteran agricultural pests. However, the application of chemical pesticides negatively impacts its development and survival. Therefore, it is essential to assess the toxicity of commonly used insecticides against T. ostriniae and evaluate their compatibility. This study aims to determine the toxic effects of five common insecticides (dinotefuran, abamectin, imidacloprid, beta‐cypermethrin, and chlorantraniliprole) on the development, reproduction, and enzymatic activity of T. ostriniae. The contact, lethal, and developmental toxicities were evaluated. Activities of detoxification enzymes, including cytochrome P450 (CYP450), carboxylesterase (CarE), and glutathione S‐transferase (GST), and protective enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) as well as malondialdehyde (MDA) and reactive oxygen species (ROS), mitochondrial respiratory chain complex I (MRCC I), adenosine triphosphate (ATP) of T. ostriniae were examined after being treated with the five insecticides. The results showed that the order of lethal toxicity in adult T. ostriniae was beta‐cypermethrin > dinotefuran > imidacloprid > abamectin > chlorantraniliprole. The emergence rates of adult T. ostriniae exposed to insecticides during the egg and larval stages were higher than those exposed to insecticides during the prepupal and pupal stages. The activities of CYP450, GST, and SOD were increased, but CarE activity and ROS content were decreased in T. ostriniae treated with the five insecticides compared with the control. Beta‐cypermethrin increased the POD and CAT activities. Chlorantraniliprole decreased CAT activity and increased MDA content. The MRCCI of T. ostriniae was not significantly affected by any of the five insecticides tested. The ATP content of T. ostriniae was not significantly affected by chlorantraniliprole but was significantly decreased by the other four insecticides. In conclusion, the toxicities of the five insecticides to T. ostriniae were different, among which imidacloprid, dinotefuran, abamectin, and beta‐cypermethrin had a high risk of toxicity to T. ostriniae, and chlorantraniliprole had a low risk to T. ostriniae. [ABSTRACT FROM AUTHOR]