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The effect of inhibitors on the electron flow triggering photo-phobic reactions in Cyanophyceae.

1. Since photo-phobic reactions in the blue green alga Phormidium uncinatum seem to be triggered by changes of electron flow rates into or out of an electron pool situated in the electron transport chain between photo-system II and I, the effect of inhibitors affecting the electron transport chain has been studied. 2. Dose response curves of the phobic reaction have been measured by varying the trap energy in double beam light trap experiments with constant pairs of monochromatic light. From these dose response curves the effects of the inhibitors on both types of phobic reactions, i.e. exit reactions and entrance reactions, have been calculated. 3. Dibromothymoquinone (DBMIB) inhibits the electron transport between the electron pool and photosystem I by preventing the reoxidation of plastoquinone. The phobic entrance reaction, which results in an emptying of the light trap, is triggered by changes in the electron flow out of the pool; thus it is more effected by DBMIB than the exit reaction, which is mediated by the electron transport into the pool. 4. The phobic exit reaction, which results in accumulations in the light trap, is triggered by changes in the electron flow into the electron pool via photosystem II. 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) inhibits the electron transport near photosystem II; thus it affects the exit reaction more than the entrance reaction.

Cell Movement

The effect of diuredosan on Echinococcus granulosus and Taenia hydatigena infections in dogs.

Diuredosan has been tested against Echinococcus granulosus and Taenia hydatigena infections in dogs. The drug showed significant activity against T hydatigena, but there was no significant dose response curve against E granulosus in this trial. Two treatments at 50 mg/kg or 100 mg/kg, however, reduced the number of dogs infected with hydatid worms. Worms were still present in some dogs after three treatments at 50 mg/kg. Vomiting and diarrhoea were relatively common sequelae at and above 50 mg/kg.

Animals

Anthelmintic control of concurrent Hymenolepis nana and Syphacia obvelata infections in the mouse with uredofos.

Tests were made to determine the efficacy of uredofos in either the diet or drinking water for controlling induced Hymenolepis nana and naturally acquired Syphacia obvelata infections in the mouse. Four levels of administration (50, 75, 100, and 125 parts per million) were used in a 6-day drugdiet assay. Consistent removal of Hymenolepis nana occurred only at 125 parts per million, whereas removal Syphacia obvelata was complete at all levels. The disodium salt of uredofos was given in the drinking water. Three levels of administration (12, 18 and 25 mg/kg) were used, and the treatment period was limited to 24 hours. Complete removal of Hymenolepis nana occurred at 25 mg/kg and Syphacia obvelata was completely eliminated at all levels.

Administration, Oral

Contributions to ecological chemistry CXII1. Balance of conversion of buturon-14C in wheat under outdoor conditions.

The urea herbicide buturon (N-[p-chlorophenyl]-N'-methyl-N'-isobutinyl-urea), 14C-labeled, was sprayed on winter wheat as an aqueous formulation (2.98 kg/ha) under outdoor conditions. Upon harvest (three months after application), a total of 49.2% of the applied radiocarbon was recovered: 2.0% in the plants, 46.9% in the soil, and 0.3% in the leaching water (depth greater than 50 cm); less than 0.1% was in the grains (0.464 ppm). Only about half of the radioactivity present in plants could be recovered under mild extraction conditions; about half of this was unchanged buturon. In straw and husk extracts, the following metabolites were identified by gaschromatography/mass spectrometry:N-(p-chlorophenyl)-N-methyl-O-methyl-carbamate (metabolite I), N-phenyl-N'-formyl-urea (metabolite II), two unstable metabolites giving (p-chlorophenyl)-isocyanate upon purification (metabolites III and IV), N-(p-chlorophenyl)-N'-methyl-N'-isobutenylol-urea (metabolite V), p-chloroformanilide (metabolite VI) and biologically bound p-chloroaniline (metabolite VII). In the root and basal stem extract, the following metabolites were identified by gas chromatography/mass spectrometry: N-(p-chlorophenyl)-O-methyl-carbamate (metabolite VIII) and N-(p-chlorophenyl)-N'-methyl-urea (metabolite IX).

Chromatography, Gas

[On the phytotoxicity of some N 1-phenyl-N 1- alkylureas].

A series of N1-phenyl-N1-alkylureas (E) and a series of N-carbamoyl derivatives of tetrahydroquinoline (D) were prepared and studied for phytotoxicity. The substances studied (Tables I, II, substances i leads to xxvii) were mostly new compounds and were prepared from suitable secondary amines by condensation with alkylating agents. Biological tests involved pre- and post-emergence treatment of five common weeds with doses of 6 kg/ha and lower doses (Tables i, ii). The tetrahydroquinoline derivatives (I leads to VII) proved inactive except for the N-dimethylcarbamoyl derivative (III) which on foliar absorption showed selective phytotoxicity against Vicia sativa L. Most of the members of the N1-phenyl-N1-alkylurea class (VIII leads to XXVII) did not have wide spectrum phytotoxicity. Some compounds have however interesting specificity of action against Vicia sativa L.

Alkylation

[Toxicity of benzhydrylurea under experimental conditions].

Benzhydrylurea, which displays an anticonvulsant action and is of low acute toxicity in capable after a 3-month administration to rats to inhibit the growth of male-rats, intensify the excretion of protein with the urine, raise the blood sugar level (with its single administration--to reduce), provoke dystrophic changes in the liver, kidneys and central nervous system. Following a 1--3-week introduction of the substance guinea pigs and cats demonstrate hemorrhagic erosions in the stomach and small intestine (but not rabbits, dogs and rats), the appearance of pathological forms of erythrocytes, while guinea pigs suffer from leucopoietic disorders.

Animals

A manual method for applying the Hansch approach to drug design.

A procedure is described in which an initial small group of compounds is selected, tested, and ordered according to potency. The potency order in the group is then compared to the tabulated potency order calculated for various parameter dependencies relating to hydrophobic, electronic, and steric effects. From this activity pattern analysis the probable operative parameters can be deduced and a new substituent selection made for the synthesis of potentially more potent analogues. Application of the method is illustrated with a series of examples. It differs from a previously described decision tree, single compound stepwise approach in that it involves the batchwise analysis of small groups of compounds, usually the preferred procedure for logistical reasons if the compounds are relatively easy to synthesize.

Alcohol Oxidoreductases

Antihypertensive activity of some novel pyridinylidene arylurea derivatives in spontaneously hypertensive rats.

3 novel pyridinylidene arylurea derivatives were found to lower arterial pressure in spontaneously hypertensive rats. Their relative oral potency ranged from 6 to 32 times that of guanethidine. The onset of antihypertensive action following their oral administration was less than 1 h and the duration of action ranged from 8 to over 24 h. The antihypertensive activity of the pyridinylidene arylureas was found to be assoicated with depletion of tissue catecholamines. Compound C depleted cardiac norepinephrine with little or no effect on total brain norepinephrine levels. It is suggested that compound C may have useful antihypertensive properties without CNS depressant activity.

Animals

Magnolol Potentiates Sorafenib-induced Apoptosis and Inhibits Metastatic Signaling in Renal Carcinoma.

BACKGROUND/AIM: Sorafenib is a standard targeted therapy for renal cell carcinoma; however, resistance and limited efficacy remain clinical challenges. Magnolol, a bioactive compound derived from Magnolia officinalis, exhibits anti-cancer properties, and may enhance therapeutic responses. This study investigated whether magnolol potentiates the anti-tumor effects of sorafenib in murine renal carcinoma (Renca) cells and explored the underlying molecular mechanisms. MATERIALS AND METHODS: Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and drug interactions were analyzed using the Chou-Talalay method. Apoptosis was evaluated by Annexin V/propidium iodide (PI) staining, cell-cycle analysis, and caspase activation. Western blotting and flow cytometry were performed to examine apoptotic pathways and epidermal growth factor receptor (EGFR)/SRC proto-oncogene, non-receptor tyrosine kinase (SRC)/nuclear factor kappa B (NF-&#x3ba;B) signaling. Transwell assays and protein expression profiling were used to analyze migration, invasion, and epithelial-mesenchymal transition (EMT) markers. RESULTS: Combination treatment synergistically reduced cell viability, with a combination index (CI) <1, and significantly enhanced apoptosis via activation of intrinsic and extrinsic pathways. Co-treatment suppressed EGFR/SRC proto-oncogene, SRC/ NF-&#x3ba;B signaling and reduced migration, invasion, and EMT-associated markers. CONCLUSION: Magnolol enhances sorafenib efficacy by promoting apoptosis and inhibiting survival and metastatic signaling pathways in renal carcinoma cells.

Lignans