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Journal of Medicinal Chemistry Apr 2006A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold...
A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to 1 (NSC-639829), against cancer cell lines. 6n was more effective than 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM.
Topics: Antineoplastic Agents; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Phenylurea Compounds; Pyrimidines; Structure-Activity Relationship; Tubulin Modulators
PubMed: 16570932
DOI: 10.1021/jm051261s -
Pest Management Science Feb 2004Residue levels and degradation rates of five benzoylphenylurea insecticides were studied in zucchinis and peppers grown in experimental greenhouses in Almería (Spain)....
Residue levels and degradation rates of five benzoylphenylurea insecticides were studied in zucchinis and peppers grown in experimental greenhouses in Almería (Spain). Benzoylphenylurea residues were analyzed by HPLC using on-line post-elution photoirradiation with fluorescence detection. Mathematically defined decline curves were established by determining optimal relationships between benzoylphenylurea residues and time, using different models. The models that best fitted the experimental data were those of first-order for diflubenzuron, triflumuron, hexaflumuron and flufenoxuron in zucchini and RF first-order models for the five insecticides in peppers and for lufenuron in zucchini. Half-life times for the residues on the two vegetables were estimated from the optimal models. In order to guarantee safe consumption of the two vegetables, we have estimated suitable pre-harvest intervals complying with the maximum residue levels established by the Spanish Government. In all cases, such pre-harvest intervals were shorter than those specified by the manufacturers of commercial formulates. Experimental data for the five insecticides in peppers and for lufenuron in zucchini were also fitted to a first-order model. Even though this function was legitimized statistically, estimations of decline times (T/2) and pre-harvest intervals were quite different from those provided by the optimal model.
Topics: Benzamides; Capsicum; Chromatography, High Pressure Liquid; Cucurbita; Diflubenzuron; Environment, Controlled; Models, Biological; Pesticide Residues; Phenylurea Compounds; Spain; Time Factors
PubMed: 14971687
DOI: 10.1002/ps.812 -
Journal of Agricultural and Food... Aug 2015Benzoylurea chitin synthesis inhibitors are widely used in integrated pest management (IPM) and insecticide resistance management (IRM) programs due to their low... (Review)
Review
Benzoylurea chitin synthesis inhibitors are widely used in integrated pest management (IPM) and insecticide resistance management (IRM) programs due to their low toxicity to mammals and predatory insects. In the past decades, a large number of benzoylurea derivatives have been synthesized, and 15 benzoylurea chitin synthesis inhibitors have been commercialized. This review focuses on the history of commercial benzolyphenylureas (BPUs), synthetic methods, structure-activity relationships (SAR), action mechanism research, environmental behaviors, and ecotoxicology. Furthermore, their disadvantages of high risk to aquatic invertebrates and crustaceans are pointed out. Finally, we propose that the para-substituents at anilide of benzoylphenylureas should be the functional groups, and bipartite model BPU analogues are discussed in an attempt to provide new insight for future development of BPUs.
Topics: Animals; Chitin; Insecta; Insecticides; Structure-Activity Relationship; Urea
PubMed: 26168369
DOI: 10.1021/acs.jafc.5b02460 -
Ecotoxicology and Environmental Safety Jul 2020Benzoylphenylureas as an important type of insect growth regulators, acting on the moulting stage in immature insects, are highly effective and low toxic. The new...
Benzoylphenylureas as an important type of insect growth regulators, acting on the moulting stage in immature insects, are highly effective and low toxic. The new benzoylphenylurea TXH09 [N-((2,6-dimethyl-4-(heptafluoropropyl-2-yl)phenyl)carbamoyl)-2,6-difluorobenzamide] has high efficacy against chewing insect pests harming vegetables and rice. In this paper, the efficacy of TXH09 against two intractable borers Ostrinia furnacalis and Grapholitha molesta were evaluated in field, and safety assessment by exploring the characteristics of photodegradation, cytotoxicity, micronucleus generation and chromosome aberration was performed. The results showed that TXH09 had good capability in preventing infested corn and reducing the population of O. furnacalis larvae, and maintained high efficacy on shoot protection and peach conservation against G. molesta larvae. There were no significant differences between the control effects of TXH09 and that of hexaflumuron or diflubenzuron at the same active dose. TXH09 photolysis in solvents N,N-dimethylformamide, toluene and methanol yielded two major products, and the photodegradation of TXH09 was more prone to occur in N,N-dimethylformamide. TXH09 and the mixture of its photoproducts showed higher cytotoxicity on insect Sf-9 cells than on human Hek293 cells. Moreover, TXH09 didn't show significant effects in inducing micronucleated cells in both male and female mice and chromosomal aberrations in mouse spermatocytes by its own. In conclusion, TXH09, as an effective insecticide, has good environmental safety performance against O. furnacalis and G. molesta in field.
Topics: Animals; Cell Survival; Female; HEK293 Cells; Humans; Insecticides; Larva; Male; Mice; Moths; Mutagenicity Tests; Phenylurea Compounds; Photolysis; Plant Diseases; Sf9 Cells
PubMed: 32283411
DOI: 10.1016/j.ecoenv.2020.110591 -
Journal of Agricultural and Food... Apr 2007New propesticides with two effects of both benzoylphenylureas and carbamates were designed and synthesized by the key intermediate N-chlorosulfenyl-N-methylcarbamate,...
New propesticides with two effects of both benzoylphenylureas and carbamates were designed and synthesized by the key intermediate N-chlorosulfenyl-N-methylcarbamate, which was prepared for the first time. These benzoylphenylurea-S-carbamates were identified by 1H NMR spectroscopy and elemental analyses. The bioactivities of the new compounds were evaluated. These benzoylphenylurea-S-carbamates exhibited excellent larvicidal activities against Oriental armyworm, some of which were good as compared to the parent benzoylphenylureas. Toxicity assays indicated that these benzoylphenylurea-S-carbamates had knockdown activities of carbamates at higher concentrations and insect growth regulator activities of benzoylphenylureas at lower concentrations. We found that the title compounds exhibited good systemic larvicidal activities against Oriental armyworm, which were especially advantageous when combating sucking pests. Some of these title compounds can kill aphids and mosquitoes as well.
Topics: Animals; Aphids; Carbamates; Culicidae; Insecticides; Larva; Lepidoptera; Magnetic Resonance Spectroscopy; Phenylurea Compounds
PubMed: 17348679
DOI: 10.1021/jf063564g -
Bioorganic & Medicinal Chemistry Letters May 2004Novel series of benzoylphenylurea analogs 7-10 were prepared and evaluated for in vitro cytotoxic activity against a panel of eight different human cancer cell lines. A...
Novel series of benzoylphenylurea analogs 7-10 were prepared and evaluated for in vitro cytotoxic activity against a panel of eight different human cancer cell lines. A very interesting inhibition profile against BxPC3, Mia-Paca, and Hep2 cells with compound 10 has been observed. Compounds 8 and 9 showed the significant cytotoxicity in Hep2 cells. All cell lines were resistant to compound 7.
Topics: Antineoplastic Agents; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Magnetic Resonance Spectroscopy; Phenylurea Compounds
PubMed: 15081011
DOI: 10.1016/j.bmcl.2004.02.019 -
European Journal of Cell Biology Mar 2009Chitin is an essential constituent of the insect exoskeleton, the cuticle, which is an extracellular matrix (ECM) covering the animal. It is produced by the...
Chitin is an essential constituent of the insect exoskeleton, the cuticle, which is an extracellular matrix (ECM) covering the animal. It is produced by the glycosyltransferase chitin synthase at the apical plasma membrane of epidermal and tracheal cells. To fulfil its role in cuticle elasticity and stiffness it associates with proteins, thereby adopting a stereotypic arrangement of helicoidally stacked sheets, which run parallel to the surface of the animal. One approach to understand the mechanisms of chitin synthesis and organisation is to dissect these processes genetically. However, since only a few genes coding for factors involved in chitin synthesis and organisation have been identified to date using the model arthropod Drosophila melanogaster insight arising from mutant analysis is rather limited. To collect new data on the role of chitin during insect cuticle differentiation, we have analysed the effects of chitin synthesis inhibitors on Drosophila embryogenesis. For this purpose, we have chosen the benzoylphenylurea diflubenzuron and lufenuron that are widely used as insect growth regulators. Our data allow mainly two important conclusions. First, correct organisation of chitin seems to directly depend on the amount of chitin synthesised. Second, chitin synthesis and organisation are cell-autonomous processes as insecticide-treated larvae display a mosaic of cuticle defects. As benzoylphenylurea are used not only as insecticides but also as anti-diabetic drugs, the study of their impact on Drosophila cuticle differentiation may be fruitful for understanding their mode of action on a cellular pathway that is seemingly conserved between vertebrates and invertebrates.
Topics: Aminoglycosides; Animals; Benzamides; Cell Membrane; Chitin; Chitin Synthase; Cytochrome P-450 Enzyme System; Diflubenzuron; Dose-Response Relationship, Drug; Drosophila Proteins; Drosophila melanogaster; Embryo, Nonmammalian; Embryonic Development; Female; Gene Expression Regulation, Developmental; Integumentary System; Larva; Mutation; Nucleotidyltransferases; Phenotype; Protein Transport
PubMed: 18996617
DOI: 10.1016/j.ejcb.2008.09.002 -
European Journal of Cancer (Oxford,... Jan 2007A phase I study of dimethylamino benzoylphenylurea (BPU), a tubulin inhibitor, was performed using a weekly continuous schedule. Patients with refractory solid tumours...
A phase I study of dimethylamino benzoylphenylurea (BPU), a tubulin inhibitor, was performed using a weekly continuous schedule. Patients with refractory solid tumours received oral BPU once weekly without interruption at doses ranging from 5 to 320mg using an accelerated titration design. Nineteen subjects received 54 cycles of BPU. Early pharmacokinetic findings of decreased clearance with increasing dose and plasma accumulation led to the expansion of the 320mg dose level. Two subjects then developed late haematologic dose-limiting toxicities (DLTs) that were associated with the highest plasma exposure to BPU and metabolites. Study enrollment resumed at dose 150mg with real-time pharmacokinetic monitoring. Seven additional subjects (6 evaluable) were treated for a median of 2 cycles (range 1.5-4) without further myelotoxicity. A long half-life and accumulation of BPU and active metabolites were observed, recommending against a continuous administration. Weekly oral BPU therapy should be further tested using an interrupted schedule.
Topics: Adult; Aged; Antineoplastic Agents; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Female; Humans; Male; Methylurea Compounds; Midazolam; Middle Aged; Neoplasms
PubMed: 17084620
DOI: 10.1016/j.ejca.2006.09.006 -
Bulletin of Environmental Contamination... Oct 2008Chinese cabbage has long been consumed as a staple food by the Koreans in various forms of fresh, salted, or fermented as kimchi. To fulfill the off-season demand for...
Chinese cabbage has long been consumed as a staple food by the Koreans in various forms of fresh, salted, or fermented as kimchi. To fulfill the off-season demand for this crop, it has become a common practice to be cultivated under greenhouse conditions. Since pesticide residues in/on leafy vegetables have strongly concerned with food safety in the Korean society, the changes of lufenuron residues, in/on Chinese cabbage applied by foliar spraying under greenhouse conditions was investigated. Lufenuron 5% emulsifiable concentrate (EC) was sprayed with diluted solution of recommended and double doses to the crop. The shoots of the cabbage were harvested immediately after spraying, and sequentially the harvests were conveyed to analyze the residual amounts. The deposited level of the analyte in/on Chinese cabbage under greenhouse conditions seemed to be difficult to produce the crop with 0.2 ppm of maximum residue limit (MRL) of the Korea Food and Drug Administration (KFDA).
Topics: Benzamides; Biomass; Brassica; Calibration; Chromatography, High Pressure Liquid; Insect Control; Insecticides; Pesticide Residues; Plant Leaves; Plant Shoots; Reference Standards; Reproducibility of Results; Solutions; Spectrophotometry, Ultraviolet
PubMed: 18592122
DOI: 10.1007/s00128-008-9490-x -
Synthesis and insecticidal activity of heptafluoroisopropyl-containing benzoylphenylurea structures.Journal of Agricultural and Food... Mar 2010Fourteen novel heptafluoroisopropyl-containing benzoylphenylureas were designed and synthesized. Their insecticidal activities against armyworm ( Pseudaletia separata...
Fourteen novel heptafluoroisopropyl-containing benzoylphenylureas were designed and synthesized. Their insecticidal activities against armyworm ( Pseudaletia separata Walker) were examined and compared with the commercial product diflubenzuron. Three compounds (IIi, IIj, and IIk) showed excellent insecticidal effect, and their activity resembled that of diflubenzuron. Compound IIi also showed nearly the same insecticidal activity as novaluron on African cotton leafworm ( Spodoptera littoralis ). Furthermore, results from a field trial indicated that 5% EC IIi exhibited similar efficacy in comparison with chlorfluazuron and hexaflumuron against imported cabbage worm ( Pieris rapae L.) and diamondback moth ( Plutella xylostella ), respectively.
Topics: Animals; Insecticides; Molecular Structure; Moths; Phenylurea Compounds
PubMed: 20014763
DOI: 10.1021/jf9025508