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At least 19 recordsLinked to original sources
PubMed1975

Structure-activity relationship in the urokinase hydrolysis of alpha-N-acetyl-L-lysine anilides.

The absence of both nonproductive binding and substrate activation and also the good solubility of the substrates make the urokinase-catalysed hydrolysis of specific anilides a very suitable reaction for substrate structure-enzyme activity studies. Derivatives of alpha-N-acetyl-L-lysine anilide with high sigma minus-value substituents in the aniline ring were synthesized. Rate constants kappa-cat. and apparent Michaelis-Menten constants K-m (app.) are presented. From the substituent dependence of kappa-cat. and from the fact that kappa-cat. is 13 to 37 times smaller than the deacylation rate constant it is concluded that the rate-limiting step proceeds prior to deacylation. The catalytic rate constant kappa-cat. obeys a linear free-energy relationship of the Hammett type with Q equals +0.72. Two different mechanisms implied by the results obtained from the model reaction (specific base and general acid-base catalysed hydrolysis of N-acetylglycine anilides under extreme conditions) are proposed in order to account for this positive and low Q-value. In the first mechanism the breakdown of an enzyme tetrahedral intermediate is rate-limiting, while in the second one its formation controls the overall rate. The discrimination between the two mechanisms, however, could not be found.

Anilides↗
PubMed1992

Toxic response of linoleic acid anilide in female rats.

The toxicity of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) was studied in female rats. Female Sprague-Dawley rats were given 250 mg/kg of LAA or HLAA in mineral oil, by gavage, on alternate days for two weeks. Control rats received an equal volume of mineral oil. The animals were sacrificed at day 1, 7 and 28 following the last dose. Organ-to-body weight ratio was increased for spleen in both LAA and HLAA treated rats at day 1. Lung, kidney and brain showed increases in this ratio at some time point, whereas, thymus in the HLAA group showed a decrease at day 28. Among blood parameters, red blood cells and hemoglobin content decreased in both LAA and HLAA treated groups at day 1 and in the LAA group at day 7. Serum IgA levels increased throughout the study in both treatment groups and were more pronounced in HLAA treated rats. Splenic T-helper lymphocyte numbers decreased in the HLAA group at day 1, whereas, other cell types were not affected. The changes observed in female rats are comparable to our previous findings in male rats and relatively minor in relation to sex differences. These results further support that hemopoietic system is an early target of fatty acid anilide toxicity.

Anilides↗
PubMed1976

[Microbial breakdown of acid anilide fungicides (author's transl)].

o-Toluylanilide, 2.5-dimethylfuran-3-carboxanilide, 5.6-dihydro-2-methyl-1.4-oxathiine-3-carboxanilide and other acid anilides are systemic fungicides which act selectively on rusts and smuts. From garden soil a Nocardia sp. was isolated which can grow with acid anilide fungicides as the only source of carbon. From this Nocardia sp. it was possible to produce mutants which are blocked genetically at various steps of the breakdown pathway of these acid anilide fungicides. It was possible to follow the breakdown pathway with the aid of accumulates of the rough I strain and of the mutants as well as by growth and enzyme tests. Breakdown starts with hydrolytic splitting of the acid amide bond by an acylamidase. The acid components of the fungicides are accumulated in the medium; they do not affect the growth. The aniline component is oxidized to pyrocatechol by a dioxygenase. Methyl and chloro-derivatives of aniline which are formed in the soil due to the hydrolysis of herbicides and fungicides, are also converted into the respective pyrocatechol derivatives. By orthocleavage cis-cis muconic acid forms from pyrocatechol. This compound is metabolized into succinate and acetyl CoA via the beta ketoadipate pathway.

Amidohydrolases↗
PubMed1979

New antiarrhythmic agents. 3. Primary beta-amino anilides.

The synthesis and pharmacologic evaluation of primary beta-amino anilides, as well as comparisons with tocainide, lidocaine, and its beta homologue, are described. Substituted anilines were acylated with 3-bromoacyl chlorides and converted to the title compounds by direct amination or via 3-phthalimido anilides and subsequent hydrazinolysis. Alternatively, anilines were acylated with substituted acryloyl chlorides and the amines prepared by addition of ammonia to the double bond. The target compounds were evaluated for their ability to protect against chloroform-induced fibrillation in mice. All were found to have some antifibrillatory activity; several were more potent than tocainide, a compound in clinical trials as an oral antiarrhythmic drug. Four compounds were tested for their effects against ventricular arrhythmias in dogs with myocardial infarction. 3-Amino-2',6'-butyroxylidide (38) was found to be more potent and less CNS toxic than tocainide.

Anilides↗
PubMed1992

Effect of fatty acid anilides on immune responses of Swiss mice.

The possible relationship between fatty acid anilides and the toxic oil syndrome (TOS) which appeared in Spain in 1981 has been debated during recent years. These anilides have been detected as anomalous compound in toxic oils analysed. After treatment with one daily dose of 50 mg/kg of oleilanilide (88.86% pure) for 5 days, animals showed a tendency towards progressive loss of body weight and a significant increase in serum concentration of immunoglobulins. The percentage of suppressor T cells in spleen diminished significantly compared with the control group. Consequently, an increase in the helper T cells/suppressor T cells was also observed. The production of IgM and IgG in culture was significantly higher than in controls and no differences were seen in IgA synthesis. The functional studies of generation of specific IgM, IgA and IgG suppressor cells at variable doses of concanavalin A (Con A) showed paradoxical behaviour of suppressor T cells generated by low doses of Con A. A similar change occurred at higher doses of Con A. These results suggest that low-dose treatment with oleilanilides induces an alteration in the immune response in Swiss mice.

Anilides↗
PubMed1978

Catalysis and leaving group binding in anilide hydrolysis by chymotrypsin.

The influence of the leaving group on the reactivity of specific anilides in alpha-chymotrypsin-catalyzed hydrolysis (chymotrypsin, EC 3.4.21.2) involves both its binding to the enzyme (steric effect) and electronic nature (electronic effect). These effects are considered in terms of the stereoelectronic theory for the formation and cleavage of the tetrahedral intermediate in acyltransfer reactions. The application of this theory to the enzyme hydrolysis leads to the conclusion that the nature of the reaction products and the effectiveness of the catalysis are controlled by the orientation of the leaving group nitrogen lone pair orbital. The leaving group binding affects the formation of a reactive conformation of the enzyme tetrahedral intermediate that is presumed to intervene between the Michaelis complex and the acylenzyme. The steric and electronic effects could be separated in a straightforward fashion only in the case of equal binding of the leaving groups to the leaving-group-binding site of alpha-chymotrypsin.

Anilides↗
PubMed1979

New antiarrhythmic agents. 1. Primary alpha-amino anilides.

Thirty-two alpha-amino anilides with various substituents in the aromatic ring and in the alpha position are described. Their abilities to protect mice against chloroform-induced fibrillation and to elicit toxicity were determined. Substitution of an alkyl or aryl group in the alpha position enhanced the antifibrillatory activity. In most cases, increased potency was accompanied by increased toxicity. Eleven compounds were tested in dogs with surgically induced myocardial infarction; most showed antiarrhythmic activity. 2-Aminopropiono-2',6'-xylidide, tocainide, was chosen for clinical investigation.

Anilides↗
PubMed1975

Kinetic studies of carboxypeptidase Y. III. Action on ester, amide, and anilide substrates and the effects of some environmental factors.

Kinetic parameters of carboxypeptidase Y are given for the hydrolyses of ester, amide, and anilide substrates. The kcat/Km values were compatible with those of chymotrypsin [EC 3.4.21.1] with a few exceptions. One ionizable group with a pK of around 5.8 was suggested to be involved in the free enzyme in hydrolyzing all the substrates, including peptide substrates. In addition, hydroxylaminolysis and the kinetic isotope effects of deuterium oxide indicated, with some reservations, a reaction mechanism which proceeds via the formation of an acyl intermediate.

Amides↗
PubMed1978

Studies on the use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline for the synthesis of acylamino acid anilides and p-nitroanilides.

The use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) for coupling acyl-L-amino acids with aniline and p-nitroaniline has been investigated. Optically pure anlides are obtained in good yield but partial racemization occurred in one case. p-Nitroanlides cannot be obtained under similar conditions but if the reaction solvent is removed and the residue left for several days, coupling occurs giving a racemic product in moderate yields. Reaction mechanisms are proposed on the basis of isolated and characterized intermediates. It has been found that N-benzoylamino acid anilides and p-nitroanilides are cleaved within a few minutes by hydrogen bromide in acetic acid to give the N-benzoylamino acid and the amine.

Amino Acids↗
PubMedDate not supplied

Spasmolytic activity of two synthetic anilide local anaesthetics.

Two basic anilides EA-7 and EA-8 were investigated for their antispasmodic activity against a variety of spasmogens on different tissues from different species of animals and comparison was made with lignocaine. EA-8 was found to be the most potent in this respect, followed by EA-7 and lignocaine. The antispasmodic potency does not correspond to their local anaesthetic potency. This suggests a direct depressant effect on tissues.

Acetylcholine↗
PubMed1976

Cryoenzymology of chymotrypsin: the detection of intermediates in the catalysis of a specific anilide substrate.

The reaction between chymotrypsin and N-acetyl-L-phenylalanine p-nitroanilide has been studied at subzero temperatures in fluid aqueous dimethyl sulfoxide solvent. Following initiation of the reaction at temperatures as low as -90 degrees C, a series of four reactions prior to the normal rate-limiting step (acylation) was detected spectrophotometrically. Various experimental observations have led to the following interpretation of these reactions. Reaction 1 corresponds to the binding of substrate yielding the initial Michaelis complex. Reactions 2 and 3 are two pH-independent reactions, ascribed to substrate-induced changes in the positions of active-site groups. Reaction 4 is a pH-dependent reaction (pK = 5.9) which involves the imidazole of His-57 but which is not the formation of a tetrahedral intermediate, oxazolinone, or acyl enzyme. The slowest detected step corresponded to the acylation reaction. No evidence for the accumulation of a tetrahedral intermediate was obtained. Spectral, kinetic, and thermodynamic data for these reactions are presented, as is justification for the relevance of these findings to the reaction under physiological conditions. These results demonstrate the utility of subzero temperatures in enzyme mechanism studies, especially with regard to allowing the accumulation of intermediates which may be quite stable at appropriate values of pH and low temperature.

Anilides↗
PubMedDate not supplied

Further studies of metyrapone effects upon anilide hydroxylation.

The enhancing effect of metyrapone upon the p-hydroxylation of acetanilide has been confirmed with the use of a new gas-chromatographic method for the determination of acetaminophen. This effect has been shown not to be due to inhibition of hydrolysis of acetaminophen or interference with its determination, or to preferential formation of other phenolic metabolites. This effect of metyrapone is remarkably substrate-specific: phenol formation from the homologues of acetanilide, formanilide and propionanilide, and that from the sulfonamide analog of acetanilide, methanesulfonanilide, is inhibited by metyrapone over the concentration range in which acetanilide hydroxylation is enhanced. The same substrate specificity was observed when the modifier was acetophenone. alpha,alpha'-Dipyridyl, however, enhances phenol formation from all three carbonacylanilides, but does not affect that from methanesulfonanilide.

2,2'-Dipyridyl↗