PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “ACETANILIDE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1991

Acetanilide 4-hydroxylase and acetanilide 2-hydroxylase activity in hepatic microsomes from induced mice.

A simple and sensitive method for the separation of 14C-labelled acetanilide, 4-hydroxyacetanilide, 3-hydroxyacetanilide and 2-hydroxyacetanilide was developed using thin-layer chromatography. This separation is the basis for the assay of acetanilide 4-hydroxylase and acetanilide 2-hydroxylase activity in liver microsomes from DBA2/N male mice that had been treated with phenobarbital, 3-methylcholanthrene, isosafrole or n-butylbenzodioxole. Microsomes were incubated with [14C]acetanilide and extracted with benzene and ethyl acetate. The extract was applied to silica gel plates and developed with a hexane/isopropanol/ammonium hydroxide/water solvent system. The radiolabelled phenolic metabolites and the parent compound were detected using a Berthold Automatic TLC Linear Analyzer. Although the 4-hydroxylated metabolite was the primary product detected, this method can be used to detect other phenolic metabolites.

Acetanilides↗
PubMed1979

Effect of halogenated benzenes on acetanilide esterase, acetanilide hydroxylase and procaine esterase in rats.

1,2,4-Trichlorobenzene, 1,3,5-trichlorobenzene, hexachlorobenzene, 1,2,4-tribromobenzene, 1,3,5-tribromobenzene and hexabromobenzene were compared for their abilities to induce acetanilide esterase, acentailide hydroxylase and procaine esterase. Except for hexabromobenzene all induced acetanilide esterase whereas the hydroxylation of acetanilide was seen only with the fully halogenated benzenes and with 1,3,5-tribromobenzene. Hepatic procaine esterase activity was increased by the three chlorinated benzenes and 1,2,4-tribromobenzene.

Acetanilides↗
PubMed2001

X-ray investigations of sulfur-containing fungicides. IV. 4'-[[Benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide.

The conformations of the two approximately isomorphous structures 4'-[[benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide, C(22)H(18)ClN(3)O(4)S, and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide, C(23)H(21)N(3)O(5)S, are stabilized by resonance-assisted intramolecular hydrogen bonds linking the hydrazone moieties and sulfonyl groups. The stronger bond is observed in the former compound. The difference in electronic properties between the Cl atom and the methoxy group is too small to significantly alter the non-bonding interactions of the sulfonyl and beta-carbonyl groups.

Acetanilides↗
PubMed1975

Acetanilides: effects on invertebrate neurons correlated with analgesic activity in vertebrates.

Identified neurons in the buccal ganglion of the marine mollusc Navanax inermis were used to examine the effects of acetanilides on neuronal membrane properties. Acetanilides increased the membrane potential and conductance of these neurons in a dose-dependent, reversible manner. These events would have the effect of decreasing membrane excitability. Acetanilides increased the slope of the curve of membrane potential as a function of log [K+]o from 33 to 58 mV decade change in [k+]o and decreased the transient depolarization observed upon reducing [Cl]o. These results indicate that acetanilides increase membrane potential and conductance by increasing the potassium conductance of the membrane relative to the chloride conductance. The variation in membrane potential as a function of external alkali-cation concentrations was used an as indirect measure of alkali-cation permeability. Acetanilides altered the relative cation permeability from Rb (1.25) greater than K (1.0) greater than Cs (0.60) greater than NaequalsLi (0.07) to K (1.0) greater than Rb (0.71) greater than Cs (0.31) greater than NaequalsLi (0.00). This shift in relative cation permeability is interpreter, in terms of Eisenman's theory of membrane permselectivity, as indicating that acetanilides increase the anionic field strength of the membrane. The ability of acetanilides to increase membrane potential or alter permselectivity is directly correlated with octanol-water partition coefficient (r equals 0.96), indicating that hydrophobicity per se can account for almost all of the activity. Steric factors are unimportant. Analysis of published experiments on acetanilide analgesia in mice reveals that hydrophobicity can also account for much of the activity in that system. Results obtained in the molluscan system may thus provide insight into the ionic, biophysical and physicochemical mechanisms underlying acetanilide-induced analgesia.

Acetanilides↗
PubMed1977

The measurement of acetanilide in plasma by spectrophotometric and selected ion monitoring methods.

Plasma samples from volunteers who had received an oral dose of acetanilide have been analysed by gas chromatography mass spectrometry and ultraviolet absorption techniques. The gas chromatography mass spectrometry method involved extraction of the plasma and analysis of the acetanilide using selected ion monitoring with a deuterated internal standard. In the ultraviolet method the plasma was hydrolysed with acid to convert the acetanilide to aniline, and this compound was diazotized and coupled with N-1-naphthylethylene-diamine. The absorbance of the resulting complex was read at 550 nm. Acetanilide levels in plasma determined by the selected ion monitoring method were significantly lower than those measured by spectrophotometry. Pharmacokinetic data calculated from the results obtained using these two assays are very different and illustrate the need for an accurate and specific method of analysis. The major metabolites of acetanilide are shown not to interfere with these assays and the results suggest the possible presence of a new metabolite of acetanilide.

Acetanilides↗
PubMed1993

Different structure of the complexes of two cytochrome P-450 isozymes with acetanilide by 1H-NMR relaxation and spectrophotometry.

The functional and spectral characteristics of the interaction of acetanilide with phenobarbital- and methylcholanthrene- induced rat liver microsomes, as well as with corresponding major isozymes (cytochromes P-450b and P-450c) have been compared. The magnitude of the reverse 1st type binding spectra proved to be negatively correlated with the acetanilide oxidation on isozymes under study. The data on paramagnetic relaxation of acetanilide protons in the presence of P-450 have shown the structure of the enzyme-substrate complex to be different for two isozymes, acetanilide molecule being closer to Fe ion in the active site in the case of P-450c, which is active towards acetanilide oxidation. For the P-450c-acetanilide complex the group oxidized (phenyl) is the closest to Fe ion.

Acetanilides↗
PubMed2003

Examination of molecular interaction sites of acetanilides with organic matter surrogates using nuclear magnetic resonance techniques.

The dynamics of acetanilide pesticide interactions with organic matter (OM) surrogates were examined using nuclear magnetic resonance (NMR) spectroscopy. Differences in the relative changes in (13)C and (1)H spin-lattice relaxation times (T(1)) were measured at multiple molecular sites of metolachlor and the probe compound acetanilide to identify interaction sites and/or surfaces between the molecules and dissolved and colloidal OM surrogates. The decrease in T(1) at specific sites of acetanilide molecules was a function of the OM used and its concentration. High-affinity interactions at nonaromatic sites of metolachlor and acetanilide were observed with cellulose, chitin, and collagen, but interactions with lignin occurred with less site specificity and involved both aromatic and nonaromatic sites of the molecules. Changes in relaxation were compared to calculated and experimentally determined binding coefficients (K(oc)). The T(1) relaxation of the aromatic sites of acetanilides showed better relations with K(oc) than the nonaromatic sites. This study shows that NMR relaxation measurements can identify the high-affinity molecular interaction sites of acetanilides to OM surrogates.

Acetamides↗
PubMed1991

Role of cytochrome P450 IA2 in acetanilide 4-hydroxylation as determined with cDNA expression and monoclonal antibodies.

The role of P450 IA2 in the hydroxylation of acetanilide was examined using an inhibitory monoclonal antibody (MAb) 1-7-1 and vaccinia cDNA expression producing murine P450 IA1 (mIA1), murine P450 IA2 (mIA2), or human P450 IA2 (hIA2). Acetanilide hydroxylase (AcOH) activity was measured using an HPLC method with more than 500-fold greater sensitivity than previously described procedures. This method, which does not require the use of radioactive acetanilide, was achieved by optimizing both the gradient system and the amount of enzyme needed to achieve detection by uv light. MAb 1-7-1 inhibits up to 80% of the AcOH activity in both rat liver microsomes and cDNA expressed mouse and human P450 IA2. MAb 1-7-1, which recognizes both P450 IA1 and P450 IA2, completely inhibits the aryl hydrocarbon hydroxylase (AHH) activity of cDNA expressed in IA1. The inhibition of only 80% of the AHH activity present in MC liver microsomes by MAb 1-7-1 suggests that additional P450 forms are contributing to the overall AHH activity present in methylcholanthrene (MC)-liver microsomes as MAb 1-7-1 almost completely inhibits the AHH activity of expressed mIA1. Maximal inhibition of IA2 by 1-7-1 results in an 80% decrease in acetanilide hydroxylase activity in both liver microsomes and expressed mouse and human IA2. The capacity of MAb 1-7-1 to produce identical levels of inhibition of acetanilide hydroxylase activity in rat MC microsomes (80%) and in expressed mouse (81%) and human P450 IA2 (80%) strongly suggests that P450 IA2 is the major and perhaps the only enzyme responsible for the metabolism of acetanilide. These results demonstrate the complementary utility of monoclonal antibodies and cDNA expression for defining the contribution of specific P450 enzymes to the metabolism of a given substrate. This complementary approach allows for a more precise determination of the inhibitory capacity of MAb with respect to the metabolic capacity of the target P450.

Acetaminophen↗
PubMed2004

The effect of carbon surface chemical composition on the adsorption of acetanilide.

The study of acetanilide adsorption-desorption performed at three temperatures (300, 310, and 320 K) and at two pH levels (7.0 and 1.5) on the series of D43/1 carbons (initial and modified with HNO3, fuming H2SO4, and gaseous NH3) is reported. Sorption data are additionally supplemented with the results of thermal analysis and calorimetric and kinetic measurements. It is shown that, generally, acetanilide adsorption at the neutral pH level is reversible (only on the more acidic carbons and at the lowest temperature does hysteresis occur due to the formation of hydrogen bonds with surface OH groups), and it decreases for the chemically modified carbons. In contrast, at the acidic pH level acetanilide adsorption is irreversible. A mechanism of irreversibility is proposed and it is shown that hysteresis is caused by the chemical reaction between the nucleophile (carbon) and the protonized acetanilide molecules. For all studied carbons, at the acidic pH level, adsorption increases and this is caused by the weakly basic character of acetanilide molecule. Adsorption results are described applying adsorbability and Dubinin-Astakhov, quasi-Freundlich and solution analogue of the Toth adsorption isotherm equations. Using the kinetic data, the effective diffusion coefficients and the energy of diffusion are calculated. It is shown that the diffusion is mainly a surface process, and the contribution of the pore diffusion increases with the rise in temperature. By applying different correlations between the parameters obtained from the theoretical description of experimental data and those characterizing the chemical composition of the studied carbons, the role of the latter in the adsorption and kinetics of acetanilide adsorption is determined.

Journal Article↗
PubMed1979

Bioassay of 4'-(chloroacetyl)-acetanilide for possible carcinogenicity.

A bioassay for the possible carcinogenicity of 4'-(chloroacetyl)-acetanilide was conducted using Fischer 344 rats and B6C3F1 mice. 4'-(Chloroacetyl)-acetanilide was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of 4'-(chloroacetyl)-acetanilide were, respectively, 2,000 and 1,000 ppm for rats and 10,000 and 5,000 ppm for mice. The compound was administered for 87 weeks of a 102-week period in rats and for 90 weeks of a 105-week period in mice. Mice were killed at the end of the last week of compound administration, while rats were observed for 1 week after compound administration ceased. There were no significant positive associations between the concentration of 4'-(chloroacetyl)-acetanilide administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression was observed for males and females of both species, indicating that the concentrations of 4'-(chloroacetyl)-acetanilide administered to the animals in this bioassay may have approximated the maximum tolerated concentrations. None of the statistical tests for any site in rats of either sex or in male mice indicated a significant positive association between compound administration and tumor incidence. Although there was a significant positive association between the concentration of the compound administered and the incidences of hepatocellular adenomas in female mice, the Fischer exact comparisons were not significant. Under the conditions of this bioassay, 4'-(chloroacetyl)-acetanilide was not carcinogenic when administered in the diet to Fischer 344 rats or B6C3F1 mice of either sex.

Journal Article↗
PubMed2001

Research strategies for design and development of NSAIDs: clue to balance potency and toxicity of acetanilide compounds.

Despite the fact that many modern drug therapies are based on the concept of enzyme inhibition, inhibition of several enzymes leads to pathological disorders. Clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) bind to the active site of the membrane protein, cyclooxygenase (COX) and inhibit the synthesis of prostaglandins, the mediators for causing inflammation. At the same time, inhibition of hepatic cysteine proteases by some NSAID metabolites like NAPQI is implicated in the pathogenesis of hepatotoxicity. As a part of our efforts to develop new effective NSAIDs, a comprehensive investigation starting from synthesis to the study of the final metabolism of acetanilide group of compound has been envisaged with appropriate feedback from kinetic studies to enhance our knowledge and technical competency to feed the know-how to the medicinal chemist to screen out and design new acetanilide derivatives of high potency and low toxicity. Structure-function relationship based on the interaction of acetanilide with its cognate enzyme, cyclooxygenase has been studied critically with adequate comparison with several other available crystal structures of COX-NSAID complexes. Furthermore, to make the receptor based drug design strategy a novel and comprehensive one, both the mechanism of metabolism of acetanilide and structural basis of inhibition of cysteine proteases by the reactive metabolite (NAPQI) formed by cytochrome P450 oxidation of acetanilide have been incorporated in the study. It is hoped that this synergistic approach and the results obtained from such consorted structural investigation at atomic level may guide to dictate synthetic modification with judicious balance between cyclooxygenase inhibition and hepatic cysteine protease inhibition to enhance the potential of such molecular medicine to relieve inflammation on one hand and low hepatic toxicity on the other.

Acetanilides↗
PubMed1989

The relation of age to the acute effects of ethanol on acetanilide disposition.

The activity of the major drug-metabolizing enzymes, the mono-oxygenases, can be inhibited by an acute dose of ethanol. We set out to determine whether age has any relation to the degree of inhibition produced by ethanol, using acetanilide as a model substrate. Eight healthy young subjects (mean age 26 years) and eight healthy elderly subjects (mean age 72 years) were studied on two occasions, once receiving acetanilide alone and once acetanilide with 75 ml vodka (30 g ethanol). The clearance of acetanilide was significantly lower (p less than 0.05) in the elderly subjects at 27 +/- 3 l/h compared to 38 +/- 2 l/h in young subjects. No age-related differences in peak blood ethanol concentrations or ethanol elimination rates were noted. After ethanol, acetanilide clearance fell 18% to 31 +/- 3 l/h in young subjects (p = 0.05) and by 15% to 23 +/- 2 l/h in elderly subjects (p = 0.08). This suggests that the elderly do not suffer greater impairment of drug oxidation after acute ethanol ingestion than do the young.

Acetanilides↗
PubMed2006

Towards an understanding of the molecular mechanism of solvation of drug molecules: a thermodynamic approach by crystal lattice energy, sublimation, and solubility exemplified by paracetamol, acetanilide, and phenacetin.

Temperature dependencies of saturated vapor pressure for the monoclinic modification of paracetamol (acetaminophen), acetanilide, and phenacetin (acetophenetidin) were measured and thermodynamic functions of sublimation calculated (paracetamol: DeltaGsub298=60.0 kJ/mol; DeltaHsub298=117.9+/-0.7 kJ/mol; DeltaSsub298=190+/-2 J/mol.K; acetanilide: DeltaGsub298=40.5 kJ/mol; DeltaHsub298=99.8+/-0.8 kJ/mol; DeltaSsub298=197+/-2 J/mol.K; phenacetin: DeltaGsub298=52.3 kJ/mol; DeltaHsub298=121.8+/-0.7 kJ/mol; DeltaSsub298=226+/-2 J/mol.K). Analysis of packing energies based on geometry optimization of molecules in the crystal lattices using diffraction data and the program Dmol3 was carried out. Parameters analyzed were: (a) energetic contribution of van der Waals forces and hydrogen bonding to the total packing energy; (b) contributions of fragments of the molecules to the packing energy. The fraction of hydrogen bond energy in the packing energy increases as: phenacetin (17.5%)<acetanilide (20.4%)<paracetamol (34.0%). Enthalpies of evaporation were estimated from enthalpies of sublimation and fusion. Activity coefficients of the drugs in n-octanol were calculated from cryoscopic data and by estimation of dilution enthalpy obtained from solubility and calorimetric experiments (for infinite dissolution). Solubility temperature dependencies in n-octanol and n-hexane were measured. The thermodynamic functions of solubility and solvation processes were deduced. Specific and nonspecific solvation terms were distinguished using the transfer from the "inert" n-hexane to the other solvents. The transfer of the molecules from water to n-octanol is enthalpy driven for paracetamol; for acetanilide and phenacetin, entropy driven.

1-Octanol↗
PubMed1982

The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications.

Acetanilides↗
PubMedDate not supplied

Novel chromatographic separation and carbon solid-phase extraction of acetanilide herbicide degradation products.

One acetamide and 5 acetanilide herbicides are currently registered for use in the United States. Over the past several years, ethanesulfonic acid (ESA) and oxanilic acid (OA) degradation products of these acetanilide/acetamide herbicides have been found in U.S. ground waters and surface waters. Alachlor ESA and other acetanilide degradation products are listed on the U.S. Environmental Protection Agency's (EPA) 1998 Drinking Water Contaminant Candidate List. Consequently, EPA is interested in obtaining national occurrence data for these contaminants in drinking water. EPA currently does not have a method for determining these acetanilide degradation products in drinking water; therefore, a research method is being developed using liquid chromatography/negative ion electrospray/mass spectrometry with solid-phase extraction (SPE). A novel chromatographic separation of the acetochlor/alachlor ESA and OA structural isomers was developed which uses an ammonium acetate-methanol gradient combined with heating the analytical column to 70 degrees C. Twelve acetanilide degradates were extracted by SPE from 100 mL water samples using carbon cartridges with mean recoveries >90% and relative standard deviations < or =16%.

Acetanilides↗
PubMed2003

Reactions of the ionized enol tautomer of acetanilide: elimination of HNCO via a novel rearrangement.

The reactions of ionised acetanilide, C(6)H(5)NH(=O)CH(3)(.+), and its enol, C(6)H(5)NH(OH)=CH(2)(.+), have been studied by a combination of tandem mass spectrometric and computational methods. These two isomeric radical cations have distinct chemistries at low internal energies. The keto tautomer eliminates exclusively CH(2)=C=O to give ionised aniline. In contrast, the enol tautomer loses H-N=C=O, via an unusual skeletal rearrangement, to form predominantly ionised methylene cyclohexadiene. Hydrogen atom loss also occurs from the enol tautomer, with the formation of protonated oxindole. The mechanisms for H-N=C=O and hydrogen atom loss both involve cyclisation; the former proceeds via a spiro transition state formed by attachment of the methylene group to the ipso position, whereas the latter entails the formation of a five-membered ring by attachment to the ortho position. The behaviour of labelled analogues reveals that these two processes have different site selectivities. Hydrogen atom loss involves a reverse critical energy and is subject to an isotope effect. Surprisingly, attempts to promote the enolisation of ionised acetanilide by proton-transport catalysis were unsuccessful. In a reversal of the usual situation for ionised carbonyl compounds, ionised acetanilide is actually more stable than its enol tautomer. The enol tautomer was resistant to proton-transport catalysed ketonisation to ionised acetanilide, possibly because the favoured geometry of the encounter complex with the base molecule is inappropriate for facilitating tautomerisation.

Journal Article↗