A pH-responsive MOF-functionalized hollow mesoporous silica controlled herbicide delivery system exhibits enhanced activity against ACCase-herbicide-resistant weeds.

BACKGROUND: Weeds grow aggressively in agricultural fields, leading to reduced crop yields and an inability to meet the growing demand for food. Herbicides are currently the most effective method for weed control. However, the overuse of herbicides has resulted in the evolution of resistance mutants and has caused environmental pollution. Therefore, new technologies are urgently required to address this global challenge. RESULTS: We report a copper-benzene-1,4-dicarboxylate metal organic framework (Cu-BDC MOF)-functionalized carboxyl hollow mesoporous silica (HMS-COOH) delivery system for the pH-controlled release of the acetyl-CoA carboxylase (ACCase)-inhibiting herbicide quizalofop-p-ethyl (QE). The delivery system (QE@HMS@Cu-BDC) enabled the efficient control of barnyard grasses that are susceptible and resistant to ACCase-inhibiting herbicides, which showed 93.33% and 88.33% FW control efficacy at 67.5 g ha-1 , respectively. With the lowest pH value (3), QE and copper ion were released slowly to total 70.30% and 78.55% levels (respectively) from QE@HMS@Cu-BDC after 89 h. QE@HMS@Cu-BDC showed better absorption, conduction, transportation and ACCase activity inhibition performance than that of QE emulsifiable concentrate (EC) in both susceptible and ACCase-herbicide resistant barnyard grasses. In addition, with the safener effect of carrier HMS@Cu-BDC and the aid of the safener fenchlorazole-ethyl (FE), the application of QE@HMS@Cu-BDC was shown to mitigate the damage caused by QE to rice plants. CONCLUSION: This work found that the new material HMS-COOH@Cu-BDC can be used to mitigate herbicide-induced oxidative stress and improve rice plant safety. Futhermore, the QE@HMS-COOH@Cu-BDC constructed in this research might be used as an efficient nanopesticide formulation for weed controls in paddy rice fields. © 2023 Society of Chemical Industry.

Phenyl imidazolidin-2-ones antagonize a ß-adrenergic-like octopamine receptor in diamondback moth (Plutella xylostella).

BACKGROUND: The diamondback moth (Plutella xylostella) is one of the most destructive lepidopteran pests on cruciferous vegetables. However, resistance has emerged to current chemical and biological insecticides used for P. xylostella control, indicating the necessity of screening new targets on P. xylostella, and finding new insecticides against P. xylostella. In particular, octopamine receptors are representative G protein-coupled receptors found only in invertebrates and are potential targets for identifying novel insecticides. RESULTS: A ß-adrenergic-like octopamine receptor gene (PxOA2B1) was cloned, and its pharmacological characteristics in P. xylostella were studied. The results demonstrated that octopamine could activate the PxOA2B1 receptor, with a half-maximal effective concentration (EC50 ) of 49.5 nm. Amitraz, an insecticide and acaricide, and its metabolite (N-2,4-dimethylphenyl-N'-methylformamidine; DPMF) were also found to act as PxOAB1R agonists. We synthesized phenyl imidazolidin-2-one derivatives 3a-h using DPMF as the lead compound, and compounds 3a-h showed similar antagonist activities as phentolamine, mianserin and chlorpromazine. In particular, 3d, with an EC50 of 25.2 nm, showed very similar antagonist activity to mianserin. CONCLUSION: This research found that PxOAB1R might be a potential target for P. xylostella control. Phenyl imidazolidin-2-ones could be novel potential antagonists targeted at octopamine receptors and would be useful tools for the design and development of novel insecticides. © 2021 Society of Chemical Industry.

Pharmacological characterization of a ß-adrenergic-like octopamine receptor in Plutella xylostella.

The ß-adrenergic-like octopamine receptor (OA2B2) belongs to the class of G-protein coupled receptors. It regulates important physiological functions in insects, thus is potentially a good target for insecticides. In this study, the putative open reading frame sequence of the Pxoa2b2 gene in Plutella xylostella was cloned. Orthologous sequence alignment, phylogenetic tree analysis, and protein sequence analysis all showed that the cloned receptor belongs to the OA2B2 protein family. PxOA2B2 was transiently expressed in HEK-293 cells. It was found that PxOA2B2 could be activated by both octopamine and tyramine, resulting in increased intracellular cyclic AMP (cAMP) levels, whereas dopamine and serotonin were not effective in eliciting cAMP production. Further studies with series of PxOA2B2 agonists and antagonists showed that all four tested agonists (e.g., naphazoline, clonidine, 2-phenylethylamine, and amitraz) could activate the PxOA2B2 receptor, and two of tested antagonists (e.g., phentolamine and mianserin) had significant antagonistic effects. However, antagonist of yohimbine had no effects. Quantitative real-time polymerase chain reaction analysis showed that Pxoa2b2 gene was expressed in all developmental stages of P. xylostella and that the highest expression occurred in male adults. Further analysis with fourth-instar P. xylostella larvae showed that the Pxoa2b2 gene was mainly expressed in Malpighian tubule, epidermal, and head tissues. This study provides both a pharmacological characterization and the gene expression patterns of the OA2B2 in P. xylostella, facilitating further research for insecticides using PxOA2B2 as a target.

Discovery of a Manduca sexta Allatotropin Antagonist from a Manduca sexta Allatotropin Receptor Homology Model.

Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behavior. They have been identified as candidate targets for next-generation insecticides, yet these targets have been relatively poorly exploited for insect control. In this study, we present a pipeline of novel Manduca sexta allatotropin (Manse-AT) antagonist discovery with homology modeling, docking, molecular dynamics simulation and structure-activity relationship. A series of truncated and alanine-replacement analogs of Manse-AT were assayed for the stimulation of juvenile hormone biosynthesis. The minimum sequence required to retain potent biological activity is the C-terminal amidated octapeptide Manse-AT (6-13). We identified three residues essential for bioactivity (Thr4, Arg6 and Phe8) by assaying alanine-replacement analogs of Manse-AT (6-13). Alanine replacement of other residues resulted in reduced potency but bioactivity was retained. The 3D structure of the receptor (Manse-ATR) was built and the binding pocket was identified. The binding affinities of all the analogs were estimated by calculating the free energy of binding. The calculated binding affinities corresponded to the biological activities of the analogs, which supporting our localization of the binding pocket. Then, based on the docking and molecular dynamics studies of Manse-AT (10-13), we described it can act as a potent Manse-AT antagonist. The antagonistic effect on JH biosynthesis of Manse-AT (10-13) validated our hypothesis. The IC50 value of antagonist Manse-AT (10-13) is 0.9 nM. The structure-activity relationship of antagonist Manse-AT (10-13) was also studied for the further purpose of investigating theoretically the structure factors influencing activity. These data will be useful for the design of new Manse-AT agonist and antagonist as potential pest control agents.

The discovery of a novel antagonist - Manduca sexta allatotropin analogue - as an insect midgut active ion transport inhibitor.

BACKGROUND: The midgut is an important site for both nutrient absorption and ionic regulation in lepidopteran larvae, major pests in agriculture. The larval lepidopteran midgut has become a potent insecticide target over the past few decades. Recent studies have shown that an insect neuropeptide, Manduca sexta allatotropin (Manse-AT), exhibits inhibition of active ion transport (AIT) across the larval midgut epithelium. The full characteristic of the AIT inhibition capacity of Manse-AT is essential to assay. In this study, AIT inhibition across the M. sexta midgut by Manse-AT and its analogues in a range of concentrations was assayed. The structure-activity relationship of Manse-AT was also studied by truncated and alanine-replacement strategies. RESULTS: Our results identified three residues, Thr4, Arg6 and Phe8, as the most important components for activity on the midgut. Replacement of Glu1, Met2 and Met3 reduced the potency of the analogues. The conservative substitution of Gly7 with alanine had little effect on the potency of the analogues. We demonstrated for the first time that Manse-AT (10-13) behaves as a potent antagonist in vitro on active ion transport across the epithelium of the posterior midgut in M. sexta. CONCLUSION: Structure-activity studies of Manse-AT are useful in developing lead compounds for the design and testing of synthetic antagonists, ultimately to develop potent and specific pest control strategies. Manse-AT (10-13) has been discovered as the first Manse-AT antagonist, with a significant effect and a short sequence compared with other insect neuropeptides. It may be a new potential pest control agent in the future. © 2016 Society of Chemical Industry.

Design, synthesis and biological activity of peptidomimetic analogs of insect allatostatins.

Allatostatins (ASTs) comprise a family of insect neuropeptides isolated from cockroaches and found to inhibit the production of juvenile hormone (JH) by the corpora allata (CA). For this reason, the ASTs can be regarded as possible IGR candidates for pest control. Six peptidomimetic analogs according to the C-terminal pentapeptide of ASTs were prepared by solid-phase organic synthetic methods in an attempt to obtain new simple substitution agents. Assays of inhibition of JH biosynthesis in vitro by corpora allata from the cockroach Diploptera punctata showed that the activity of analog I (IC(50): 0.09 µM) was more active than that of the C-terminal pentapeptide (Tyr-Xaa-Phe-Gly-Leu-NH(2), IC(50): 0.13 µM) it mimicked and the activity of the analog II (IC(50): 0.13 µM) proved roughly equivalent to the C-terminal pentapeptide. The results indicate that a new simple mimicry for Tyr-Xaa-Phe-Gly has been discovered; analog I may be a novel compound candidate for potential IGRs. This study will be useful for the design of new AST analogs for insect management.