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In this work, a method for the analysis of benzoylurea insecticides, including hexaflumuron, flufenoxuron, lufenuron and chlorfluazuron, in tea samples by high-performance liquid chromatography with Fe3 O4 -hyperbranched polyester nanocomposite as the adsorbent for magnetic solid-phase extraction was developed. The magnetic nanocomposite was prepared and characterized by infrared spectroscopy, vibrating sample magnetometry, and scanning electron microscopy. The as-prepared nanocomposite was used as a sorbent for the extraction and preconcentration of pesticide residues in tea samples. The extraction and desorption conditions, including mass ratios of raw materials, amount of sorbent, pH value, extraction time, and desorption time, were investigated. Under the final conditions chosen for the analysis, good linearity was obtained for all the tested compounds, with R2 values of at least 0.9979. The limits of detection were determined in the range of 0.15-0.3 μg/L. The recovery obtained from the analysis of tea samples with various spiked concentrations was between 90.7 and 98.4%, with relative standard deviations (n = 4) lower than 4.1%. Furthermore, the present approach was successfully applied to the quantitative determination of residues of benzoylurea insecticides in real samples.

New classes of alkylated hetarylpropylguanidines with different functionality and variation in spacer length were synthesized to determine their behavior at the four histamine receptor (H1R, H2R, H3R, H4R) subtypes. Alkylated guanidines with different terminal functional groups and varied basicity, like amine, guanidine and urea were developed, based on the lead structure SK&F 91486 (2). Furthermore, heteroatomic exchange at the guanidine structure of 2 led to simple analogues of the lead compound. Radioassays at all histamine receptor subtypes were accomplished, as well as organ bath studies at the guinea pig (gp) ileum (gpH1R) and right atrium (gpH2R). Ligands with terminal functionalization led to, partially, highly affine and potent structures (two digit nanomolar), which showed up a bad selectivity profile within the histamine receptor family. While the benzoylurea derivative 144 demonstrated a preference towards the human (h) H3R, S‐methylisothiourea analogue 143 obtained high affinity at the hH4R (pKi=8.14) with moderate selectivity. The molecular basis of the latter finding was supported by computational studies.

Diflubenzuron (DFB) and fenuron (FEN) are benzoylurea and phenylurea pesticides, widely used in Senegal, that do not exhibit any natural fluorescence, but can be determined by means of photoinduced fluorescence (PIF) methods. Photodegradation of DFB and FEN yielded a number of fluorescent and non-fluorescent photoproducts. For both pesticides, at least 10 photoproducts were detected and identified by gas chromatography-mass spectrometry (GC/MS). To identify the formed fluorescent DFB and FEN photoproducts, their fluorescence spectra were compared with those of standard compounds, including phenol and p-hydroxyaniline.

The benzoylurea chitin synthesis inhibitor teflubenzuron, widely used against sea lice in North Atlantic aquaculture, may pose an environmental threat to non-targeted crustaceans. In this experiment, laboratory acclimated pink shrimp (Pandalus montagui), a species found in fjords with Atlantic salmon farming, were exposed to dietary teflubenzuron for 46 days (control; low dose: 0.01 μg/g; high dose: 0.1 μg/g). The exposure doses represent 0.1% and 1% of a standard treatment dose for Atlantic salmon. Mortality and prevalence of deformities, pharmacokinetics, oxidative stress and transcriptomic and metabolomic profiling were used to assess the response to teflubenzuron exposure. Mortality in the high-dose group was 25% (five of 20 individuals). No control or low-dose group shrimps died. Phenotypic responses,i.e., leg deformities (0 control, 6 low, 8 high) and cloudy eyes (0 control, 3 low, 7 high), were observed in some surviving shrimps (control n = 15, low n = 17, high n = 15). Accumulated levels of teflubenzuron in shrimps from the high-dose group ranged from 4.7 to 369 ng/g wet weight. Transcriptomic profiling showed very few significantly altered genes in the exposed shrimps. Teflubenzuron-induced changes to the metabolome pointed to well-known effects of benzoylurea agents, with reduced levels of N-acetylglucosamine indicating an effect on chitin synthesis. The metabolomic profiling showed that teflubenzuron exposure was associated with reduced energy metabolism. Some metabolites pointed to increased necrosis and/or bacterial overgrowth in the teflubenzuron-exposed shrimps. In conclusion, this study shows that teflubenzuron causes phenotypic effects in P. montagui exposed to 0.1% of the treatment dose given to Atlantic salmon.

A magnetic polytriphenylamine porous organic polymer was prepared through simple self-polycondensation of triphenylamine followed by coprecipitation with Fe2+ and Fe3+ . It was applied as a magnetic adsorbent for the extraction of six benzoylurea insecticides from tomato, cucumber, and watermelon samples before their high-performance liquid chromatography and mass spectral detection. Under the optimized experimental conditions, the established method gave a low limit of detection ranging from 0.05 to 0.1 ng/g and a good linear response ranging from 0.2 to 40 ng/g with coefficients of determination >0.99. The method recoveries for spiked analytes at the concentrations of 3 and 15 ng/g in real samples were in the range of 87.7-106.7% with the relative standard deviations

Background Rice sheath blight is a globally important rice disease. Unfortunately, this critical disease has not been effectively controlled, and the intensive and continuous use of the same fungicide might increase the risk of resistance development in the pathogen. To discover new active agents against rice sheath blight, in this study, three series of β-carboline urea, benzoylurea and benzoylthiourea derivatives were designed, synthesized and evaluated for in vitro and in vivo fungicidal activity against Rhizoctonia solani. Results All these compounds (EC50 : 0.131-1.227 mmol L-1 ) exhibited better fungicidal activity than harmine itself (EC50 : 2.453 mmol L-1 ). Significantly, compound 17c (EC50 : 0.131 mmol L-1 ) displayed the best efficacy in vitro and superior fungicidal activity compared with validamycin A (EC50 : 0.397 mmol L-1 ). Moreover, the in vivo bioassay also indicated that compound 17c could be effective for the control of rice sheath blight. Conclusion Based on the bioassay result and quantitative structure-activity relationship (QSAR) information, structure modification in β-carboline warrants further investigation and its benzoylurea derivative 17c, which showed the best fungicidal activities, could emerge as a potential fungicide against rice sheath blight. © 2018 Society of Chemical Industry.

In this work, a magnetic β-cyclodextrin polymer was successfully prepared and used as an adsorbent for the magnetic solid-phase extraction of six benzoylurea insecticides (diflubenzuron, triflumuron, hexaflumuron, teflubenzuron, flufenoxuron, and chlorfluazuron) from honey, tomato, and environmental water samples. The influence of the main experimental conditions on the extraction was studied. Under the optimized conditions, the β-cyclodextrin polymer@Fe3 O4 showed an excellent extraction performance for the benzoylurea insecticides. A good linearity was obtained for the analytes in the range of 3.0-800 ng/g for honey samples, 0.3-160 ng/g for tomato samples, and 0.1-80.0 ng/mL for water samples, with the correlation coefficients above 0.9998. Satisfactory repeatabilities were achieved, with the relative standard deviations less than 5.7%. The limits of detection (S/N = 3) of the method for the benzoylurea insecticides were 0.2-0.8 ng/g for honey samples, 0.04-0.10 ng/g for tomato samples, and 0.02-0.05 ng /mL for water samples. The method was successfully used for the determination of the six benzoylurea insecticides residues in honey, tomato, and environmental water samples with a satisfactory result.

BACKGROUND In many cases, resistance alleles have been associated with fitness costs and are often dependent on environmental factors such as temperature. Here, we studied the effects of temperature on the overall fitness, including development, survival and reproduction, of three insecticide-resistant and one susceptible strain of diamondback moth (DBM), Plutella xylostella (L.). RESULTS The broader cross-resistance profile of the resistant strains previously selected by diamide and benzoylurea insecticides was tested. Cohort studies were conducted in the laboratory at three different temperatures (20 ± 1 °C, 25 ± 1 °C and 30 ± 1 °C), and involved fitness costs were estimated. We observed significant differences in the development time, with the susceptible strain showing a shorter developmental period from egg stage to adult stage compared with the resistant strains. Moreover, the resistant strains differed significantly between one another. Additionally, the population growth parameters varied among the strains, with the benzoylurea-resistant strain showing the highest costs affecting the overall fitness of this strain. A temperature of 30 °C was unfavourable for DBM development, resulting in a reduced fitness in all strains. CONCLUSION Benzoylurea selection pressure on a diamide-resistant P. xylostella strain resulted in lowest reproduction parameters and the longest generation time, as well as doubling the time among all strains tested. This suggests significant effects on the overall fitness and population growth parameters for diamide-resistant populations pressured by benzoylureas under applied conditions. © 2017 Society of Chemical Industry

A β-cyclodextrin-modified attapulgite composite was prepared and used as a dispersive micro-solid-phase extraction sorbent for the determination of benzoylurea insecticides in honey samples. Parameters that may influence the extraction efficiency, such as the type and volume of the eluent, the amount of the sorbent, the extraction time and the ionic strength were investigated and optimized using batch and column procedures. Under optimized conditions, good linearity was obtained for all of the tested compounds, with R(2) values of at least 0.9834. The limits of detection were determined in the range of 0.2-1.0 μg/L. The recoveries of the four benzoylurea insecticides in vitex honey and acacia honey increased from 15.2 to 81.4% and from 14.2 to 82.0%, respectively. Although the β-cyclodextrin-modified attapulgite composite did not show a brilliant adsorption capacity for the selected benzoylurea insecticides, it exhibited a higher adsorption capacity toward relatively hydrophobic compounds, such as chlorfluazuron and hexaflumuron (recoveries in vitex honey samples ranged from 70.0 to 81.4% with a precision of 1.0-3.7%). It seemed that the logPow of the benzoylurea insecticides is related to their recoveries. The results confirmed the possibility of using cyclodextrin-modified palygorskite in the determination of relatively hydrophobic trace pharmaceutical residues.

A simple, sensitive, and efficient method of using a pipette vial to perform dispersive liquid-liquid microextraction based on the solidification of floating organic droplets was coupled with high-performance liquid chromatography (HPLC) and a diode array detector for the preconcentration and analysis of four benzoylurea insecticides in fruit juice. In this method, 1-dodecanol was used as an extractant, and a snipped pipette was used as an experimental vial to simplify the procedure of collecting and separating solidified extractant. The experimental parameters were optimized using a Plackett-Burman design and one-factor-at-a-time method. Under the optimal conditions in the water model, the limits of detection for analytes varied from 0.03 to 0.28 μg/L, and the enrichment factors ranged from 147 to 206. Linearity was achieved for diflubenzuron and flufenoxuron in a range of 0.5-500 μg/L, for hexaflumuron in a range of 1-500 μg/L, and for triflumuron in a range of 5-500 μg/L. The correlation coefficients for the analytes ranged from 0.9986 to 0.9994 with recoveries of 91.4-110.9%. Finally, the developed technique was successfully applied to fruit juice samples with acceptable results. The relative standard deviations of the analytes at two spiking levels (50 and 200 μg/L) varied between 0.2 and 4.5%.

Diflubenzuron and teflubenzuron are benzoylureas that are used in aquaculture to control sea lice. Flubenzurons have low toxicity to many marine species such as fish and algae but by their nature are likely to have significant adverse effects on nontarget species such as crustaceans and amphipods. Although the exact mechanism of toxicity is not known, these compounds are thought to inhibit the production of the enzyme chitin synthase during molting of immature stages of arthropods. These chitin synthesis inhibitors are effective against the larval and pre-adult life stages of sea lice. Due to their low solubility and results of recent monitoring studies conducted in Norway, the sediment compartment is considered the most likely reservoir for these compounds and possible remobilization from the sediment to benthic crustaceans could be of importance. For this reason, the epibenthic copepod Tisbe battagliai was selected for investigations into the acute and developmental effects of these compounds. For comparative purposes, azamethiphos was investigated to identify differences in sensitivity and act as a negative control for developmental effects at environmentally relevant concentrations. Standard acute studies with adult copepods showed little or no acute toxicity at milligrams per liter levels with the flubenzurons, whereas a naupliar developmental test demonstrated that environmentally relevant concentrations (e.g., nanograms per liter) caused a complete cessation of molting and finally death in the exposed copepods.

In this work, a novel liquid-phase microextraction approach using nonwoven polypropylene as the extraction solvent holder was developed. Nonwoven polypropylene, a hydrophobic material, is widely used in the cleanup of oil spills. Due to its large surface area, efficient, and full extraction can be achieved. Nonwoven polypropylene containing an ionic liquid was used to extract benzoylurea insecticides (diflubenzuron, teflubenzuron, flufenoxuron, and chlorfluazuron) through vortex-assisted liquid–liquid microextraction. The parameters that affected the extraction efficiency included the type and volume of the extractant, the extraction time, the time and solvent volume for desorption and the mass and surface area of the nonwoven polypropylene. Under the optimized conditions, good linearity was obtained, with coefficients of determination greater than 0.9996, and the limit of detections of these compounds, calculated at S/N = 3, were in the range of 0.73–5.0 ng/mL. The recoveries of the four insecticides at two spiked levels ranged from 93.3 to 102.0%, with relative standard deviations of less than 4.0%. The proposed method was then successfully used for the rapid determination of benzoylurea insecticides in spiked real water samples before liquid chromatographic analysis. The procedure is simple, inexpensive, easy to execute, and can be widely used.

Benzoylurea (BU) insecticides have contributed greatly to the output of crops. Their residue in the environment put serious threats on human health and environmental safety. In this study, we have established a new, rapid, and reliable method for the monitoring of typical BU insecticides such as diflubenzuron, flufenoxuron, triflumuron, and chlorfluazuron with dispersive liquid-liquid microextraction prior to HPLC. Chlorobenzene and ethanol were employed as the extraction solvent and disperser solvent, respectively. The possible parameters which would influence the extraction efficiency such as the kinds and volumes of extraction and disperser solvents, extraction time, sample pH, centrifuging time, and salting-out effect were optimized in detail. Under the optimal conditions, the linear range of proposed method was in the range of 1.0-70 μg/L. The detection limits varied from 0.24 to 0.82 μg/L and the precision of the method was

Chemicals are widely used in aquaculture and one of the main recipients of these analytes is the aquatic environment. The aim of this work was to develop and validate a simple and sensitive method for the determination of multiclass chemotherapeutic agents in farmed fish and shellfish using matrix solid-phase dispersion and liquid chromatography-tandem mass spectrometry. Residues of azamethiphos, three avermectins, two carbamates, and two benzoylureas were extracted from samples using silica gel as clean-up adsorbent and 0.5% acetic acid in acetonitrile as elution solvent. The extraction conditions were investigated and optimized using an experimental design. Mass spectrometry detection was carried out in positive electrospray ionization mode with multiple-reaction monitoring scan (except for benzoylurea family). Matrix-matched standards were used for the drugs quantification. Good linearity (R(2) ≥ 0.996) was observed in the range of 5-500 μg kg(-1). Limits of detection were in the range of 1.5-3.7 μg kg(-1). Recoveries from salmon samples spiked with veterinary drugs were in the range 84.9-118%. Precision was satisfactory since relative standard deviations were lower than 10.6%. The method can be successfully applied for the analysis of fish and shellfish from aquaculture.

Chitin is the most abundant natural aminopolysaccharide and serves as a structural component of extracellular matrices. It is found in fungal septa, spores, and cell walls, and in arthropod cuticles and peritrophic matrices, squid pens, mollusk shells, nematode egg shells, and some protozoan cyst walls. As prokaryotes, plants and vertebrates including humans do not produce chitin, its synthesis is considered as an attractive target site for fungicides, insecticides, and acaricides. Although no chitin synthesis inhibitor has been developed into a therapeutic drug to treat fungal infections in humans, a larger number of compounds have been successfully launched worldwide to combat arthropod pests in agriculture and forestry. This review summarizes the latest advances on the mode of action of chitin synthesis inhibitors with a special focus on those molecules that act on a postcatalytic step of chitin synthesis.

A method based on pressurized liquid extraction and LC-MS/MS has been developed for determining nine benzoylureas (BUs) in fruit, vegetable, cereals, and animal products. Samples (5 g) were homogenized with diatomaceous earth and extracted in a 22 mL cell with 22 mL of ethyl acetate at 80 degrees C and 1500 psi. After solvent concentration and exchange to methanol, BUs were analyzed by LC-MS/MS using an IT mass analyzer, which achieved several transitions of precursor ions that increase selectivity providing identification. LOQs were between 0.002 and 0.01 mg/kg, which are equal or lower than maximum residue limits established by the Codex Alimentarius. Excellent linearity was achieved over a range of concentrations from 0.01 to 1 mg/kg with correlation coefficients 0.995-0.999 (n=7). Validation of the total method was performed by analyzing in quintuplicate seven different commodities (milk, eggs, meat, rice, lettuce, avocado, and lemon) at three concentration levels (0.01, 0.1, and 1 mg/kg). The recoveries ranged from 58 to 97% and the RSDs from 5 to 19% depending on the compound and the commodity. The combination of pressurized liquid extraction with LC-MS/MS provides a sensitive and selective method for the determination of BUs in food.

The Bcl-x(L)/Bak protein-protein interaction has emerged as an important target for cancer therapy due to its role in apoptosis. Inhibition of this interaction by small-molecule antagonists induces apoptosis in unhealthy cells. Bak, a pro-apoptotic Bcl-2 protein, projects four hydrophobic side chains (V74, L78, I81, and I85), corresponding to the i, i+4, i+7, and i+11 positions of an alpha-helix, into a hydrophobic cleft on Bcl-x(L). Herein, we present a novel family of rationally designed alpha-helix mimetics with improved solubility and synthetic feasibility based on a benzoylurea scaffold. These benzoylurea derivatives favor a linear conformation stabilized by an intramolecular hydrogen bond, and are able to mimic the spatial projection of the i, i+4, and i+7 residues of an alpha-helix. The binding of the benzoylurea derivatives to Bcl-x(L) was assessed using fluorescence polarization competition assays, isothermal titration calorimetry, and (15)N-HSQC experiments. These experiments showed that these agents bind to and disrupt Bcl-x(L) with low micromolar inhibition and dissociation constants, with (15)N-HSQC experiments confirming binding to the hydrophobic pocket of Bcl-x(L) normally occupied by the Bak helix.

The coupled-column (LC-LC) system, consisting of a first column packed with internal surface reversed phase (ISRP) (50 x 4.6mm ID) and a Chrompack C18 (100 x 4.6 mm ID) as second column, allowed the simultaneous determination of five benzoylurea insecticides in dichloromethane (CH2Cl2) extracts of vegetable samples without any clean-up step. This system was combined with a photochemically induced fluorescence (PIF) post-column derivatization in order to provide strongly fluorescent photoproducts from the non-fluorescent benzoylureas. Limits of detection ranged from 0.21 to 0.98 microg L(-1) of pesticide (equivalent to 0.14-0.65 microg kg(-1) in vegetable samples) and limits of determination ranged from 4.0 to 10.0 microg L(-1) (equivalent to 2.7-6.7 microg kg(-1)). Linearity of the method was established between 2 and 1800 microg L(-1), depending upon the compound. Validation of the total method was performed by randomly analyzing recoveries of four vegetable samples (aubergine, cucumber, green bean, and tomato) spiked at two levels of concentration (10.0 and 33.3 microg kg(-1)). The combination of the LC-LC system with PIF detection provides a sensitive, selective, and rapid method for the determination of pesticides in vegetable samples at levels lower than the maximum residue levels (MRLs) established for these compounds by Spanish legislation.

Various steps in the existing procedure (Slocum, R. D., Flores, H. E., Galston, A. W. and Weinstein, L. H., Plant Physiol. (1989) 89, 512) for the analysis of agmatine as its benzoyl derivative were found to impair the quantification of agmatine, leading to irreproducible results. Degradation of benzoylated agmatine is a major factor contributing to erratic results, and two mechanisms of degradation have been observed. Firstly, benzoylagmatine undergoes a temperature‐dependent hydrolysis in alkaline solution and this reaction has a half‐life of 168 min at 22°C. Therefore, the benzoylation reaction time and temperature have to be controlled in order to ensure reliable results; a maximum yield of benzoylagmatine may be obtained after incubation for 30 min. Secondly, benzoylagmatine can undergo rapid alkali‐catalysed methanolysis with a half‐life of 12 min at 22°C. Methanolysis produces a degradation product that was originally considered to be agmatine or benzoylurea, but is probably N‐benzoylmethoxybenzamidomethylene imine. The formation of benzoylagmatine depends on the amount of benzoylchloride added since small volumes of the reagent do not exhaustively derivatize agmatine, hence leading to unreliable results. Mass spectrometry of benzoylagmatine showed that tribenzoylagmatine is the main derivative formed. The suggested modifications to the existing procedure enable the rapid and reliable determination of agmatine in various plant materials.

The benzoylurea auxiliary in (I) and (IV) facilitate the formation of macrocyclic lactams via stabilization of a cisoid amide bond, promoting rapid and high yielding ring closure via ring closing metathesis.

New organogelator, N,N'-bis(3,4,5-tridodecyloxy)benzoylurea (1), gelled organic liquid such as alcohol, hydrocabons, ethyl acetate, salad oil, terpenes, and essential and perfume oil at low concentration of gelator. The terpene and perfume gels show good release of the volatile components for a long time.

The two insecticidal benzoylurea compounds, diflubenzuron and chlorfluazuron, show large differences in their toxicity against the larvae of insects like the tobacco budworm, Heliothis virescens, or the Egyptian cotton leafworm, Spodoptera littoralis, chlorfluazuron being about 100 times more toxic. This difference is due mainly to a much faster metabolism of diflubenzuron. Its half-life within the larvae is about 5 h, compared to about 50 h for chlorfluazuron. Chlorfluazuron is also the much better ovicide of the two, following injection of the compounds into the females of H. virescens. Again the difference in the rate of metabolism is the main cause. The rate of excretion of the parent benzoylureas is relatively low, but their metabolites are excreted very quickly.

Benzamidoxime and cyanic acid react to give O-carbamoyl-benzamidoxime, and not the oxime of benzoylurea as generally admitted. 3-Phenyl-5-hydroxy-l,2,4-oxa-diazole is quantitatively formed by reacting hydroxylamine on carbamoylbenzami-dine.