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[About the decomposition of acetamide as taxonomic marker for some species of the genus pseudomonas (author's transl)].

The comparative examination of the acetamide-decompostition and of the acetamide-utilisation as sole source of carbon demonstrates that various groups of the Pseudomonas species with the same kind of reaction have to be distinguished. The acetamide-decomposition-test according to BUHLMANN et al. and the methylene-blue-reduction-test show homogeneous results. As a positive result of these tests the formation of ammonia has always been shown. An acetamide decomposition of this kind has been demonstrable with P. aeruginosa, P. acidovorans and many P. cepacia strains. On liquid mineral media containing acetamide P. fluorescens, P. putida and P. pseudomallei show growth although ammonia is not produced and the test according to BUHLMANN et al. as well as the methylene-blue-reduction-test result negatively. In all tests P. alcaligenes, P. marginata, P. caryophilli and with certain exceptions P. sutzeri and P. putrefaciens react negatively.

Acetamides

Effect of p-hydroxyacetanilide, sodium sulfate, and L-methionine on the leukemogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide.

Dietary administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide to mice for 14 weeks followed by 16 weeks of control diet resulted in a high incidence of lymphocytic leukemia and a low incidence of forestomach squamous cell papillomas. The coadministration of p-hydroxyacetanilide at a dose of 1.0% with either 250 or 500 ppm of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide resulted in inhibition of leukemogenesis, whereas when p-hydroxyacetanilide was coadministered with 1000 ppm of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide the leukemia incidence was not significantly reduced, but the latent period was prolonged. When sodium sulfate was administered with p-hydroxyacetanilide and N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide, leukemogenesis was partially restored. L-Methionine, fed in place of sodium sulfate, unblocked leukemogenicity inhibition by p-hydroxyacetanilide. None of these chemicals, p-hydroxyacetanilide, sodium sulfate, or L-methionine, significantly affected the incidence of forestomach papillomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide, although tumor incidences in all groups were low. p-Hydroxyacetanilide and sodium sulfate had no significant effect on the high incidence of stomach tumors induced by formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]hydrazide or bladder tumors induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

Acetanilides

Polyamine metabolism II: N-(Monoaminoalkyl)- and N-(polyaminoalkyl)acetamides in human urine.

TLC and high-pressure liquid chromatographic examination of the dansyl derivatives obtained from human urine indicated the presence of N-[3-[4-aminobutyl)amino]propyl]acetamide (N1-acetylspermidine), N-[4-](3-aminopropyl)amino]buryl]acetamide (N8-acetylspermidine), N-(4-aminobutyl)acetamide (N-acetylputrescine), and N-(5-aminopentyl)acetamide (N-acetylcadaverine). The ratio of N1- to N8-acetylspermidine ranged from 10.3 in the urine of a patient with hepatoma to 1.1 in the urine of a normal subject. The three cancer patients had a considerably higher ratio of N1- to N8-acetylspermidine than did the three normal subjects. These findings indicate the ratio of N1- to N8-acetylspermidine in the 24-hr urine may serve as a biochemical marker for cancer.

Acetamides

Polyamine metabolism I: Synthesis of dansyl derivatives of N-(monoaminoalkyl)- and N-(polyaminoalkyl)acetamides and elucidation in urine of a cancer patient.

The dansyl derivatives of N-(monoaminoalkyl)- and N-(polyaminoalkyl)acetamides were synthesized and unequivocally characterized. TLC of the dansyl derivatives obtained from human urine indicated the presence of N-[3-[(4-aminobutyl)amino]propyl]acetamide (N1-acetylspermidine, N-[4-[(3-aminopropyl)amino]butyl]acetamide (N8-acetylspermidine), and N-(4-aminobutyl)acetamide (N-acetylputrescine) in appreciable amounts. The dansyl derivatives of N1-acetylspermidine, N8-acetylspermidine, and N-acetylputrescine were isolated and purified using various chromatographic methods. The mass spectra of these compounds were similar to those of authentic samples, which confirmed the identity of these compounds and established the presence of N8-acetylspermidine as well as N1-acetylspermidine and N-acetylputrescine in human urine.

Carcinoma, Hepatocellular

Membrane proteins and urea and acetamide transport in the human erythrocyte.

Previous studies have shown that urea and acetamide traverse the erythrocyte membrane by way of facilitated diffusion. The nature of this selective pathway is unknown. The present studies investigate the effects of proteolytic enzymes and crosslinking agents on amide transport. Cleavage of the erythrocyte membrane surface by pronase or trypsin had no effect on urea and acetamide permeability or inhibition by phloretin. These findings suggest that the sialoglycopeptide segment of the sialoglycoproteins is not critical to urea and acetamide transport. In addition, extensive crosslinking of membrane proteins with glutaraldehyde had no effect on amide transport in the absence or presence of phloretin.

Acetamides

A theoretical study of Na+ and Mg+2 binding to the carbonyl oxygen of N-methyl acetamide.

Molecular orbital calculations (CNDO/2) are reported for the interaction of Na+ and Mg+2 with the carbonyl of a model peptide moiety (N-methyl acetamide) as a function of the C--O ... Me distance and angle and with variation in the number of ligands for the purpose of determining the steepness of the distance dependence of the binding energy and for the purpose of determining the reduction of charge on the ion with increasing numbers of ligands. The greater energy derived on divalent ion binding and the steeper distance dependence indicate that selective, divalent over monovalent, ion binding will occur whenever the liganding system can provide a coordination shell of appropriate dimension. The calculations indicate that the preferred C--O ... Me angle is not 180 degrees. Of particular note is the decrease of charge on the cation on binding to N-methyl acetamide. One ligand bound to Na+ reduces the charge from 1.0 to 0.7 electron units and four ligands bound to Mg+2 reduces the charge from 2.0 to 0.7 electron units. This is of primary significance in carrier and channel mechanisms for cation permeation of lipid membranes; and although the numerical values are qualitative, the implication is for allowance of multiple occupancy of channels by monovalent cations.

Acetamides

Changes in hepatic nuclei induced by acetamide and thioacetamide.

Rat liver nuclei were examined following intoxication with thioacetamide or acetamide. A prompt increase in nuclear size occurred with the administration of either agent. The acetamide-related change was evanescent and, by 16 hours, the nuclei did not differ from controls. Thioacetamide produced an acute enlargement during the first eight hours and a second, more prolonged increase during the next 24 hours. The enlargement noted by microscopy was also detectable in isolated nuclei by flow spectrometry. Chemical determinations on isolated nuclei appear to sample the same size population seen in situ. An increase in RNA content of thioacetamide-treated nuclei occurred during the late phase. The temporal sequence of physical and chemical change suggests that the initial increase in nuclear volume is not the result of retained macromolecular formation but may involve intracellular water and electrolyte shifts.

Acetamides

Increased incidence of carcinoma of the breast in Buffalo strain rats with one kidney ingesting N-4-(4'-fluorobiphenyl)acetamide.

The role of the kidney in carcinogenesis of the breast was studied in inbred Buffalo strain female rats ingesting 0.04% N-4-(4'-fluorobiphenyl)acetamide. The experimental groups consisted of intact female rats 5 weeks of age with both kidneys intact and female rats with a uninephrectomy. The incidence of carcinomas of the breast and the number of rats with multiple carcinomas, poorly and undifferentiated carcinomas was greater in rats with a uninephrectomy. N-4-(4'-fluorobiphenyl)acetamide and its active metabolites apparently were not excreted as rapidly in the rats with one kidney as in the animals with both kidneys intact. The metabolites were then returned to the breast and/or other organs.

Aminobiphenyl Compounds

Increased susceptibility to carcinoma of the liver in rats with one kidney ingesting N-4-(4'-fluorobiphenyl) acetamide.

The role of the kidneys in hepatic carcinogenesis was studied in inbred Buffalo strain male rats ingesting 0.04% N-4-(4'-flourobiphenyl) acetamide in the diet. Experimental groups were made up of male rats with both kidneys intact and male rats with the left kidney removed. The incidence of carcinomas of the liver and the number of rats with large carcinomas, multiple carcinomas, poorly differentiated and undifferentiated carcinomas, and metastases were greater in rats with a uninephrectomy. Apparently the animals with one kidney removed were unable to secrete the metabolites of N-4-(4'-fluorobiphenyl) acetamide as readily as the rats with both kidneys.

Aminobiphenyl Compounds

Rearrangement of N-benzyl-2-cyano-2-(hydroxyimino)acetamide.

The reduction of N-benzyl-2-cyano-2-(hydroxyimino)acetamide resulted in the formation of N-benzyl-1,2-ethanediamine and N-benzyl-N'-methyl-1,2-ethanediamine in approximately an equimolar ratio. The formation of the two unexpected products is explained by the migration of a cyano group in a Beckmann-type rearrangement.

Acetamides

Energetics of the deformation of a peptide unit. Semi-empirical molecular orbital and ab initio study of N-methyl acetamide and N-acetyl-L-alanine N-methyl amide.

The problem of non-planarity of peptide unit has been investigated using N-methyl acetamide as a theoretical model. A semi-empirical molecular orbital method: Iterative Extended Hückel Theory viz. IEHT/2 (Adams S. (1974) Doctoral dissertation, State University of New York at Buffalo, U.S.A.) and non-empirical abinitio method with minimal basis set, STO-3G (Hehre, W.J., Stewart, R.F. and Pople, J.A. (1969) J. Chem. Phys. 51, 2657-2664) were used to probe the energetics of the distortion of a planar peptide unit. Distortion of one of the peptide units in a dipeptide, N-acetyl-L-alanine N-methyl amide has also been investigated using abinitio method. The studies amply demonstrate the possibility of the existence of a non-planar peptide unit. Distortion of about 10-15 degrees is predicted to bring about very small loss in energy. The results are substantiated by results from experimental studies.

Acetamides

Complete neglect of differential overlap study of the binding of salts to N-methyl acetamide.

The complete neglect of differential overlap method is used to investigate the binding of LiF, LiCl, NaF, and NaCl to N-methyl acetamide (NMA) as a model for these ions binding to a peptide moiety. The cation (formula: see text) anion interaction is shown to result in a net residual charge on NMA, which becomes less positive as the difference in electronegativity between the anion and cation of the salt present increases. A residual charge of smaller magnitude is also found on a water molecule in the analogous system cation (formula: see text) anion, which displays this same dependence.

Acetamides

Hyperplastic and neoplastic lesions of the kidney in Buffalo rats of varying ages ingesting N-4-(4'-flurobiphenyl)acetamide.

Inbred Buffalo male and female rats 4, 12, 24, and 52 weeks of age ingested 0.04% N-4(4'-fluorobiphenyl)acetamide in a semisynthetic diet for 36 weeks. Animals were killed 12 weeks later. Male rats 24 weeks old were more susceptible to the development of carcinomas of the kidney than were female rats of the same age or younger or older animals of both sexes. Rats with renal cell carcinomas either did not have hepatic carcinomas or had small ones.

Acetamides

Histopathology of breast lesions induced in BUF rats of varying ages by ingestion of N-4-(4'-fluorobiphenyl) acetamide.

Inbred BUF male and female rats 4, 12, 24, and 52 weeks old ingested 0.04 percent N-4-(4'fluorobiphenyl)-acetamide in a semisynthetic diet for 36 weeks. They were killed 12 weeks later. Susceptibility to mammary carcinogenesis was related to the age and sex of the animals. Younger female rats developed more mammary tumors. Approximately half of these mammary tumors were well-differentiated adenocarcinomas; the remainder were either poorly differentiated or anaplastic adenocarcinomas.

Acetamides

Morphologic and biologic correlation of hyperplastic and neoplastic renal lesions occurring in Buffalo and Fischer strain rats ingesting n-4-(4'-fluorobiphenyl) acetamide.

Hyperplastic and neoplastic lesions of the kidney induced in inbred Buffalo and Fisher strain rats with 0.04% N-4-(4'-fluorobiphenyl) acetamide were transplanted s.c. to rats of the same strain. Hyperplastic renal lesions ("areas" or nodules) did not survive and grow. Carcinomas of the kidney grew and killed the animals. Growth was related to the size and the degree of differentiation of the carcinoma. It is concluded that the histologic pattern of hyperplastic and neoplastic lesions of the kidney can be correlated with the results obtained on transplantation.

Acetamides

Metabolism and disposition of N-(4-(5-nitro-2-furyl)-(2-14-C)thiazolyl)acetamide in the rat.

The metabolism of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide (NFTA), a carcinogen for the mouse, rat, dog, and hamster, was investigated in the rat. Radioactive NFTA administered ip to young and lactating female rats was rapidly absorbed through the peritoneum and deposited in the urine, intestinal contents, and feces. Less than 0.5% of the radioactivity was expired as CO2 during the first 24 hr. Two yellow metabolites, accounting for 5 and 27% of the radioactivity in the urine, were found by paper chromatography. One metabolite retained the 2-amino-4-(5-nitro-2-furyl)thiazole moiety. Less than 0.5% of the radioactivity in the urine was due to unchanged 14-C-NFTA. The radioactivity level in the visceral organs reached a maximum 2 hr after dosing and then gradually decreased. Liver contained considerably more radioactivity than did other visceral organs; this was mainly distributed in the cytosol and 900g pellets. Fifty per cent of the radioactivity in the liver was bound to the hot trichloroacetic acid (TCA)-insoluble fraction; that bound to the cold TCA-insoluble fraction increased gradually from 66.9% at 2 hr to 82.6% at 24 hr. The radioactivity bound to the cold and hot TCA-insoluble fractions in kidney remained at 30% and 20%, respectively. Nitroreduction of 14-C-NFTA by microsomes, as a prerequisite of the binding of metabolite to microsomal protein, was demonstrated. Addition of L-cysteine or reduced glutathione to the incubation mixture did not alter the nitroreductase activity of the microsomes; however, binding of radioactivity to protein was significantly decreased. Addition of other amino acids did not significantly decrease the nitroreductase activity or binding to protein. These results suggest that reduced NFTA binds to the protein sulfhydryl groups. Since 14-C-NFTA binds to macromolecules in vivo,nitroreductionmay be important for the metabolism of 5-nitrofurans.

Acetamides

Pharmacological properties of the anti-inflammatory agent pyridyl-biphenylyl-acetamide (diphenpyramide).

Pyridyl-biphenylyl-acetamide (diphenpyramide, Z-876) is a new bisphenylalcanoic derivative with marked anti-inflammatory, analgesic, antipyretic and uricosuric properties. It is more active than phenylbutazone in the adjuvant polyarthritis in the rat when given prophylactically or therapeutically. It is thrice as active as phenylbutazone and ten times as active as acetylsalicylic acid (ASA) on the carrageenin-induced edema of the hind-paw. Diphenpyramide is characterized by low acute toxicity and by weak ulcerogenic activity. On the carrageenin-induced edema the therapeutic index of diphenpyramide is 30 times higher than that of indometacin and the ratio between the ED50 and the UD50 (ulcerogenic dose in 50% of the treated rats) is 39 times higher than that of ASA.

Acetamides