PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “SULFANILAMIDE”

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 739 records · Page 41Linked to original sources

Ambulance notes of a Bellevue Hospital intern: May 1938.

In 1938, as a New York University/Bellevue Hospital intern, I recorded notes on the 384 cases I saw during my 1-month ambulance duty. Although I intended to use them to follow up the clinical course of patients I admitted to Bellevue, the long hours and pressure of work made this ambitious goal unachievable. Sixty years later, after retirement from academic medicine and medical practice at New York University School of Medicine, I found the long-lost notes among my papers. They are of historic interest since they provide insight into aspects of primary and emergency medicine of the era when the therapeutic efficacy of the sulfanilamide class of agents was under investigation, a unique view of the life of an intern just before interns were replaced on ambulances by technicians, and a glimpse of the surprising character of several neighborhoods of pre-World War II Manhattan. The notes also provide the basis for a current analysis of case incidence and treatment by disease category. A description of the confluence of social, economic, and political forces that led to the establishment of the Bellevue Hospital Ambulance Service, the first such urban service in the world, is included.

Ambulances↗

Influence of obesity on sulfonamide disposition in Zucker rats.

The genetically obese Zucker rat was used as a model of obesity and compared to its lean littermate to assess and quantify obesity-altered changes in the in vivo disposition of six sulfonamides. Body composition determination indicated that the obese rats were twice the weight of lean rats and a distinct trend towards an increase in fat free mass and total body water was observed. The sulfonamide blood concentration was measured by colorimetry after a 7 mg/kg intravenous dose. All sulfonamides exhibited a biexponential decline of blood concentration with time. The volume of distribution and clearance of sulfanilamide in lean and obese rats were similar resulting in similar elimination half-lives. A decrease in clearance coupled with a trend towards an increase in volume of distribution prolonged the elimination half-life of sulfadiazine in obese rats. For sulfapyridine, sulfamerazine, sulfisomidine and sulfisoxazole, increases in the volumes of distribution and clearances resulted in similar elimination half-lives in lean and obese rats. The free fractions of the sulfonamides were significantly increased in the serum of obese rats, the influence of which on the volume of distribution and clearance is discussed.

Animals↗

Effects of pig slurry on the sorption of sulfonamide antibiotics in soil.

Sorption of p-aminobenzoic acid (pABA) and five sulfonamide antibiotics to loess Chernozem topsoil amended with varied additions of pig slurry was investigated in batch trials. In unfertilized soil, partition coefficients (Kd) of sulfonamides ranged from 0.3 to 2.0. Strong sorption nonlinearity (1/n = 0.5 to 0.8) was best fitted by the Freundlich isotherm (R2 = 0.7 to 1.0) and was indicative for specific sorption mechanisms. Adsorption to pig slurry was much stronger, and nondesorbable portions were increased compared with soil. However, in a mixture of soil and slurry (50:1 w/w), sorption of the antibiotics was significantly decreased at a lower concentration range of pABA and the sulfonamides. This was attributed to competitive adsorption of dissolved organic matter (DOM) constituents from manure. An increase in pig slurry amendment resulted in increased total organic matter, DOM concentration, and ionic strength, but pH decreased. As a result, the nonadsorbed portions of pABA, sulfanilamide, and sulfadiazine (logD(ow) < -0.4) ranged from 47% to 82% of the applied concentration in the differently manured substrates. Dissolved fractions of the antibiotics reached a maximum at a soil-slurry ratio of 9:1 and decreased with further addition of manure. This decrease was related to the formation of less-effective DOM associates in solution. The adsorbed and desorbed portions of the less-polar substances--sulfadimidine, sulfadimethoxine, and sulfapyridine (logD(ow) > 0.1)--remained nearly constant in the presence of increased manure input. The pH changes caused by manure amendment strongly affected ionisation status of the latter compounds, thus resulting in increased adsorption, which compensated the mobilizing effect of DOM. It is suggested that the effect of manure be considered in test methods to determine the soil retention of pharmaceutical substances.

Adsorption↗

The binding of sulfonamides to horse liver alcohol dehydrogenase.

The binding of sulfonamides to the active site of horse liver alcohol dehydrogenase has been studied by their effect on affinity labelling and steady state kinetics. Affinity labelling with iodoacetate and BIP has been used to study binding to free enzyme. The unsubstituted sulfonamide, sulfanilamide (I), shows very weak binding compared to the other sulfonamides tested. Most important for binding is the type of substituent attached to the parent sulfonamide, particularly when as in sulfathiazole this is a heterocycle which binds to the catalytic zinc atom of the enzyme. For sulfathiazole the dissociation constant from the enzyme is pH dependent showing two pKa values. The lower at pH 7 is the pKa of the drug itself, while that at pH 9 agrees with the ionization of water bound to the catalytic zinc ion. Steady state kinetics have been carried out at pH 7.0 and 10.0 to examine sulfonamide binding to the enzyme when coenzyme is attached. Both NAD+ and NADH induce substrate competitive sulfonamide binding. Likewise sulfathiazole accelerates the dissociation of NADH from the enzyme and SO Vmax for alcohol oxidation. The latter like stimulation of the affinity labelling reaction with iodoacetate is considered to result from binding of the thiazole ring to the catalytic zinc ion. With all the sulfonamides examined hydrophobic binding and charge are important in determining affinity to the active site and the mode of binding. Sulfonamides containing pyrazole or imidazole rings can be important in alcohol therapy.

Affinity Labels↗

Effects of nephrotoxic compounds on active uptake of drugs in isolated renal tubules in rabbits.

The uptake of sulfonamides and phenolsulfonphthalein (PSP) was examined in vitro using isolated renal proximal tubule suspension, and the effects of nephrotoxic compounds on the uptake of sulfamethizole (SMZ) were studied. The uptake of SMZ and PSP was energy dependent and was inhibited competitively by iodopyracet (IP), which is transported actively by the p-aminohippurate mechanism. The uptake of sulfamethoxazole was also reduced by IP but that of sulfanilamide was negligible. The present results correspond well with those of in vitro experiments reported previously. Nephrotoxic compounds, mercuric chloride, neomycin, viomycin and kanamycin, decreased the uptake of SMZ non-competitively. The inhibitory action of the three antibiotics corresponds with in vivo potency, suggesting that this renal tubule preparation may provide a simple method for predicting the nephrotoxicity of drugs.

Animals↗

[3H]acetazolamide binding to carbonic anhydrase in normal and transformed cells.

The binding of [3H]acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor, to soluble and particulate forms of CA was investigated. Sources for the assays were purified CA II, adult rat cortical, oligodendrocyte and neuronal enriched preparations; cultured murine glial cells, rat C-6 glioma, rat hepatoma and human glioblastoma cells. CA enzyme activity in the same preparations was also assayed by following change in pH during incubation. A gel permeation chromatographic method was developed to assess [3H]AZ binding to soluble CA, while glass fiber filter vacuum filtration was used for particulate CA binding. Saturable specific binding of [3H]AZ to rat cortical soluble and particulate CA preparations was demonstrated. Computer-assisted data analysis estimated the binding parameters of [3H]AZ to soluble rat cortical CA to be Bmax = 0.38 +/- 0.13 pmol/mg protein and Kd = 34.7 +/- 17.5 nM. The rat cortical particulate fraction Bmax was 2.05 +/- 0.28 pmol/mg protein with a Kd of 107.1 +/- 24.2 nM. Purified bovine CA-II bound 1.15 +/- 0.19 pmol [3H]AZ/mg protein with a Kd of 54.0 +/- 3.4 nM. The pH optima for [3H]AZ binding to soluble and particulate CA was between 6.5 and 7.5. Binding was linear with respect to protein up to 1.0 mg/mL. The particulate fraction bound 3-4 times more [3H]ligand per unit protein than the soluble fraction. Interestingly, no detectable CA enzyme activity or [3H]AZ binding was observed in the soluble or particulate fractions of human glioblastoma, rat C-6 glioma or rat hepatoma cells. Binding of [3H]AZ to other soluble enzymes or proteins was negligible. In competition binding experiments, a rank order of inhibition of [3H]AZ binding to rat cortical CA by established CA inhibitors was: dichlorphenamide greater than acetazolamide greater than or equal to benzolamide greater than methazolamide greater than hydrochlorothiazide greater than or equal to sulfanilamide. [3H]AZ binding was not affected by other classes of pharmacologic characterizing agents. The binding of [3H]AZ to the CA enzyme molecule is highly specific and sensitive and may prove useful in vitro or in situ as a probe for this enzyme.

Acetazolamide↗

A modified ultraviolet spectrophotometric method for the determination of theophylline in serum in the presence of barbiturates.

Ultraviolet spectrophotometry is the most commonly used technique for the determination of theophylline levels for therapeutic monitoring. Common interferences in most methods are barbiturates and xanthines. A modified method which eliminates interferences from barbiturates and most xanthines is presented. Theophylline is extracted from serum with chloroform/isopropanol at pH 7.4 back extracted into dilute hydrochloric acid and then the solution is made alkaline with sodium hydroxide. Barbiturate interferences are eliminated. Interference from caffeine, uric acid, 7-(2,3-dihydroxypropyl)theophylline, xanthine, and hypoxanthine are not observed. Theobromine, and the metabolite 3-methylxanthine interfere. Interference is not observed from quinidine, diazepam, salicylate, glutethimide, methylprylon, propranolol, methaqualone, dilatin and ethchlorvynol. Sulfanilamide, procainamide and chlordiazepoxide interfere.

Barbiturates↗

Gastric mucosal protection by acetazolamide derivatives: role of carbonic anhydrase and sulfhydryls.

Acetazolamide, a carbonic anhydrase inhibitor, prevents acute gastric hemorrhagic lesions induced by ethanol. We used acetazolamide and other carbonic anhydrase inhibitors to correlate their gastroprotective effects with the degree of inhibition of carbonic anhydrase. Since acetazolamide is a thiadiazole, we also investigated structurally related thiadiazoles that contain sulfhydryls to test the hypothesis that the protection against ethanol-induced gastric erosions is related to the presence of sulfhydryls. Dose-response studies with acetazolamide revealed that the protection did not correlate with the inhibition of carbonic anhydrase in the rat gastric mucosa. The carbonic anhydrase inhibitors sulfanilamide and ethoxzolamide, did not offer protection. Bismuthiol I, a thiadiazole with two sulfhydryls, was twice as protective as 2-amino-5-mercapto-1,3,4-thiadiazole with only one sulfhydryl group. We conclude that the protection by acetazolamide against ethanol-induced lesions is not related to the inhibition of carbonic anhydrase in the gastric mucosa. The gastroprotective effect of acetazolamide and its derivatives may be related to their content of sulfhydryls in an oxidized or reduced state.

Acetazolamide↗

High-performance liquid chromatography-thermospray mass spectrometry of ten sulfonamide antibiotics. Analysis in milk at the ppb level.

Ten sulfonamide antibiotics including sulfanilamide (SNL), sulfamethazine (SMZ), sulfamethizole (SMTZ), sulfachloropyridazine and sulfaquinoxaline (SQX), were analyzed by thermospray (TSP) mass spectrometry on-line with a high-performance liquid chromatography-UV detection system. Except for the pairs SMZ-SMTZ and sulfadimethoxine-SQX, the standards were resolved in both the UV and TSP profiles. Co-eluting compounds could be differentiated in TSP by their different relative molecular masses. The [M+H]+ ion was the base peak for all the standards except SNL, which showed an [M+NH4]+ ion. Collision-induced dissociation of the [M+H]+ ions afforded daughter ion spectra characterized by common ions at m/z 92, 108 and 156, and ions derived from the amine substituent ([MH-155]+). TSP detection limits [signal-to-noise ratio (S/N) > 3] were below 20 ng (scan mode), 2 ng (selected reaction monitoring, daughter ions from [M+H]+) and 400 pg (selected ion monitoring). UV detection limits were ca. 2 ng (S/N > 5). Results obtained from the multi-residue analysis of spiked cow milk samples at the low ng/ml level are presented.

Animals↗

Drugs as allergens: detection and combining site specificities of IgE antibodies to sulfamethoxazole.

An immunoassay was developed for the detection of sulfamethoxazole reactive IgE antibodies in the sera of patients who experienced life threatening anaphylactic reactions following the ingestion of co-trimoxazole (trimethoprim and sulfamethoxazole). Patients who had significant levels of sulfamethoxazole reactive IgE antibodies in their sera did not have IgE antibodies that reacted with trimethoprim-Sepharose. Inhibition experiments with a number of sulfonamides to determine the fine structural specificities of the sulfamethoxazole reactive IgE antibodies in three patients revealed that sulfamethoxazole and, depending on the serum, sulfamerazine and sulfamethizole, were the most potent inhibitors of IgE binding, whereas the parent sulfonamide, sulfanilamide, was a very poor inhibitor. From a detailed examination of structure-activity relationships, we concluded that the 5-methyl-3-isoxazolyl group on the sulfamethoxazole molecule was the allergenic determinant for all three patients with the 5-methyl group being particularly important for IgE antibody recognition. The assays for the detection of IgE antibodies to sulfamethoxazole and trimethoprim should prove useful for the diagnosis of immediate hypersensitivity to co-trimoxazole and perhaps for monitoring drug therapy in AIDS patients where a high incidence of adverse reactions to co-trimoxazole has been reported.

Adult↗

1H NMR and UV-Vis spectroscopic characterization of sulfonamide complexes of nickel(II)-carbonic anhydrase. Resonance assignments based on NOE effects.

The binding of acetazolamide, p-fluorobenzensulfonamide, p-toluenesulfonamide, and sulfanilamide to nickel(II)-substituted carbonic anhydrase II has been studied by 1H NMR and electronic absorption spectroscopies. These inhibitors bind to the metal ion forming 1:1 complexes and their affinity constants were determined. The 1H NMR spectra of the formed complexes show a number of isotropically shifted signals corresponding to the histidine ligands. The complexes with benzene-sulfonamides gave rise to very similar 1H NMR spectra. The NMR data suggest that these aromatic sulfonamides bind to the metal ion altering its coordination sphere. In addition, from the temperature dependence of 1H NMR spectra of the p-fluorobenzenesulfonamide adduct, a conformational change is suggested. The T1 values of the meta-like protons of the coordinated histidines have been measured and resonance assignments based on NOE experiments were performed.

Acetazolamide↗

The performance of the local lymph node assay with chemicals identified as contact allergens in the human maximization test.

For many years, tests in the guinea pig have been the favoured option for the identification of the skin sensitization potential of chemicals. However, the mouse has been used widely in immunology research and can represent a viable alternative. A variety of murine assays have been described, including several methods based on ear swelling as an endpoint. Another option is to assess induced lymph node cell proliferation and it is this which forms the basis of the murine local lymph node assay (LLNA). The LLNA has undergone several successful interlaboratory validations and compares well with standard guinea pig assays. In the present study, the performance of the LLNA was examined with chemicals tested previously in the human maximization test (HMT). 30 chemicals, 23 of which proved positive in the HMT and seven of which were negative, have been tested. All but four of the materials found positive in the HMT also tested positive in the LLNA. Of these four, sulfanilamide and paraben esters would not classify as skin sensitizers in the guinea pig maximization test and nickel has been found to yield variable results in a number of predictive animal tests. Of the seven substances which proved negative in the HMT, six were also negative in the LLNA, the exception being sodium dodecyl sulfate. These data demonstrate that the LLNA is able to identify accurately chemicals which have the potential to cause significant allergic contact dermatitis in humans.

Allergens↗

Tobacco-specific nitrosamines in some Nigerian cigarettes.

Ten popular brands of cigarettes on the Nigerian market were analyzed for tobacco-specific nitrosamines (TSNA) in tobacco and in mainstream smoke, as well as nitrate in tobacco. TSNA was analyzed using a gas chromatography/thermal energy analyzer (GC-TEA), while nitrate was determined spectrophotometrically as nitrite following on-line reduction with copper, diozatization with sulfanilamide and coupling with N-(1-naphthyl) ethylene diamine to form an azo dye. In mainstream smoke, the concentration of NNN, NAB/NAT and NNK were respectively, between 8 and 90 ng, 10 and 65 ng, and between 15 and 72 ng/cigarette. Preformed NNN ranged between 64 and 565 ng/cigarette, while preformed NAB/NAT and NNK ranged respectively from 109 to 476 ng/cigarette, and from 55 to 317 ng/cigarette. Nitrate levels ranged between 1.5 and 6.1 mg/g tobacco. In general, the results indicate that the TSNA content of Nigerian cigarettes are within the range found for European and American cigarettes.

Nicotine↗

High-performance liquid chromatographic determination of primary aromatic amines in urine after derivatization to an azo dye with 2-aminoanthracene.

A sensitive HPLC method for the determination of primary aromatic amines (anilino compounds) is described. Samples were prepared by derivatization of the substrate to an azo dye with 2-aminoanthracene (2-AA). 2-AA was found to react with the diazonium salts prepared from substituted anilines such as 4-halo, -sulfonyl, -carboxyl, -nitro or -acetyl derivatives, but not 4-hydroxy or -alkyl derivatives. In this work, three model compounds [sulfanilamide, 4-aminobenzoyl-beta-alanine and 4-aminobenzoic acid (PABA)] were used to test the linearity and accuracy of the method. Chromatographic separation was carried out using a reversed-phase column (ODS) and ultraviolet detection at 279 nm. Good linearity for the three compounds was found within the range 50-2000 ng/ml. The intra-day coefficient of variation for the three compounds (at 100, 500, 1000 ng/ml) was below 10%. Using this method, the urinary excretion of PABA and its metabolites was studied after oral administration of PABA to rats.

Aniline Compounds↗

Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1 protease.

The human immunodeficiency virus (HIV) has been shown to be the causative agent for AIDS. The HIV virus encodes for a unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors have been useful in combating the disease. The inhibitors incorporate a variety of isosteres including the hydroxyethylurea at the protease cleavage site. We have shown that the replacement of t-butylurea moiety by benzothiazolesulfonamide provided inhibitors with improved potency and antiviral activities. Some of the compounds have shown good oral bioavailability and half-life in rats. The synthesis of benzothiazole derivatives led us to explore other heterocycles. During the course of our studies, we also developed an efficient synthesis of benzothiazole-6-sulfonic acid via a two-step procedure starting from sulfanilamide.

Administration, Oral↗

Theoretical study of gas-phase acidity, pKa, lipophilicity, and solubility of some biologically active sulfonamides.

The geometries of 19 biologically active substituted sulfonamides (including clinically useful acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, and brinzolamide) in both neutral and deprotonated forms, were optimized using Becke3LYP/6-311+G(d,p) method (compounds 1-6) and two-layered ONIOM (B3LYP 6-311+G(d,p): MNDO) method (compounds 7-19). The investigated sulfonamides are weak acids with calculated acidity of about 1320-1420 kJ mol(-1). Of acids studied the highest gas-phase acidity (1324 kJ mol(-1)) possesses methazolamide. This drug is, according to the computed pKa value (5.9), also in water solution the most acidic compound of the sulfonamides investigated. The computed pKa values varied between 5.9 and 12.6 and correlate well with the available experimental pKa's found in the literature. Cancerostatic aromatic sulfonamides 16-19 are generally weak acids with the acidity comparable or slightly lower than the lead sulfanilamide. The available experimental partition coefficients of sulfonamides investigated are best reproduced by the IA LOGP method. Computed partition coefficients for antiglaucoma sulfonamides 1-13 varied between -0.47 and 2.61 (IA LOGP). Thus these compounds are only slightly or moderate lipophilic. The lipophilicity of the cancerostatic sulfonamides 14-18 is from relatively narrow interval between -0.07 and 1.68 (IA LOGP). The most potent CAI 10-13 are also the most lipophilic compounds among the antiglaucomatics studied. The available experimental solubilities are best reproduced by the IA LOGS method. The computed solubilities qualitatively correlate with the corresponding lipophilicities, logS increasing as logP declines. The analysis of molecular descriptors defined by Lipinski have been shown that all of the sulfonamides studied obey 'Rule of 5'. Therefore, in the early stages of the design of antiglaucoma sulfonamides, it is becoming more important to determine the pKa, lipophilicity, water solubility, and other physicochemical properties associated with a drug, before synthetic work is undertaken, with the aim of avoiding the synthesis of compounds that are predicted to have poor biopharmaceutical characteristics.

Carbonic Anhydrase Inhibitors↗

Carbonic anhydrase inhibitors: the first selective, membrane-impermeant inhibitors targeting the tumor-associated isozyme IX.

The inhibition of the tumor-associated transmembrane carbonic anhydrase IX (CA IX) isozyme possessing an extracellular active site has been investigated with a series of positively-charged, pyridinium derivatives of sulfanilamide, homosulfanilamide and 4-aminoethylbenzenesulfonamide. Inhibition data for the physiologically relevant isozymes I and II (cytosolic forms) and IV (membrane-bound) were also provided for comparison. A very interesting inhibition profile against CA IX with these sulfonamides has been observed. Several nanomolar (K(i)'s in the range of 6-54 nM) CA IX inhibitors have also been detected. Because CA IX is a highly active isozyme predominantly expressed in tumor tissues with bad prognosis of disease progression, this finding is very promising for the potential design of CA IX-specific inhibitors with applications as anti-tumor agents. This is the first report of inhibitors that may selectively target CA IX, due to their membrane-impermeability and high affinity for this clinically relevant isozyme.

Antigens, Neoplasm↗

Carbonic anhydrase inhibitors: inhibition of human cytosolic isozyme II and mitochondrial isozyme V with a series of benzene sulfonamide derivatives.

Among the 14 human isozymes of carbonic anhydrase (CA, EC 4.2.1.1) presently known, the cytosolic hCA II is the most active and plays a host of physiological functions, whereas the mitochondrial hCA V is unique due to its role in several biosynthetic reactions. An inhibition study of these isozymes with a series of sulfonamides is reported here, with the scope to detect lead molecules for the design of isozyme-specific CA inhibitors (CAIs) targeting the mitochondrial isoform. Indeed, recently it has been shown that CA V is a novel target for the drug design of anti-obesity agents among others. Compounds included in this study were mainly ortho-, meta-, and para-substituted-benzenesulfonamides, together with several halogeno-substituted sulfanilamides and disubstituted-benzene-1,3-disulfonamide derivatives. Isozyme V showed an inhibition profile with these sulfonamides different of that of hCA II. Thus, IC(50) values in the range of 80 nM to 74 microM against hCA II, and 0.78-63.7 microM against hCA V with these derivatives have been obtained. Only one compound, 2-carboxymethyl-benzenesulfonamide, was more active against hCA V over hCA II (selectivity ratio of 1.39), whereas all other derivatives investigated here were much better hCA II inhibitors (selectivity ratios CA II/CA V in the range of 0.0008-0.73) than hCA V inhibitors.

Benzene Derivatives↗