Allosteric inhibition of endothelin ETA receptors by 3, 5-dibromosalicylic acid.
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Derivatives of salicylic acid (SA) and benzoic acid prevent endothelin-1 (ET-1) binding to ETA receptors. This study analyzed actions of 30 derivatives of benzoic acid and salicylic acid on (125)I-ET-1 binding to recombinant rat ETA receptors. The most active compounds were 3,5-dibromosalicylic acid (Br2SA, K(i) = 0.5 mM) and 3,5-diiodosalicylic acid (K(i) = 0.3 mM). They were about 50 times more potent than SA and aspirin. Br2SA inhibited equilibrium (125)I-ET-1 binding in an apparently competitive manner. It accelerated 8-fold the dissociation of (125)I-ET-1 receptor complexes and did not modify the second order rate constant of association of (125)I-ET-1 to its receptors. Br2SA also decreased the affinity of ETA receptors for receptor antagonists BQ-123 and bosentan. Br2SA accelerated dissociation of (125)I-ET-1-solubilized ETA receptor complexes and decreased the apparent molecular size of solubilized receptors. Br2SA and 3,5-diiodosalicylic acid inhibited two cellular actions of ET-1: the mobilization of intracellular Ca(2+) stores in isolated cells and contractions of rat aortic rings. They accelerated the relaxing action of BQ-123 and bosentan in ET-1-treated aortic rings. The results suggest the existence of an allosteric modifier site on ETA receptors that recognizes selected derivatives of SA. SA derivatives might be of therapeutic interest to relieve tight ET-1 binding and to favor actions of receptor antagonists. (+info)
Facile preparation of peracetates and per-3-bromobenzoates of alpha-mono- and disaccharides.
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A simple and convenient method for the preparation of fully acetylated and (3- bromo)benzoylated alpha-monosaccharides and disaccharides through vigorous mechanical mixing of solid reactants on a high speed shaker is described. Using this technique a variety of alpha-acylated sugars are prepared, including penta-O-acetyl-alpha-D-galactopyranose, penta-O- acetyl-alpha-D-glucopyranose, penta-O-acetyl-alpha-D-mannopyranose, octa-O-acetyl-alpha-lactose, penta-O-(3-bromo)benzoyl-alpha-D-galactopyranose, penta-O-(3-bromo)benzoyl-alpha-D-gluco- pyranose, penta-O-(3-bromo)benzoyl-alpha-D-mannopyranose, and octa-O-(3-bromo)benzoyl- alpha-lactose. (+info)
Palladium-catalyzed one-step synthesis of isoindole-1,3-diones by carbonylative cyclization of o-halobenzoates and primary amines.
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Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY.
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INTRODUCTION: Many countries have specific legislation, such as the Controlled Substances Act (1970) in the United States and the Misuse of Drugs Act (1971) in the United Kingdom to control recreational drugs. There is a growing market and supply of "novel" recreational drugs, which include the misuse of pharmaceutical compounds and research chemicals. These are often not covered under current legislation, despite the fact that they often have both similar chemical structures and/or clinical effects to controlled recreational drugs. CASE REPORT: A male patient presented to an emergency department with delayed onset of severe agitation, hallucinations, and tonic-clonic seizures following the use of Bromo-dragonFLY and an unknown white powder. He settled following IV benzodiazepines and supportive care, and was discharged with no evidence of long-term sequelae. Analysis of the white powder by gas chromatography/mass spectrometry (GC/MS), ultraviolet/visible spectrophotometry (UV/VIS) and thin layer chromatography (TLC) showed the presence of Bromo-dragonFLY (1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane); serum analysis by GC/MS and liquid chromatography with tandem mass spectrometry (LC/MS/MS) confirmed that a combination of Bromo-dragonFLY (0.95 ng/mL), ketamine (20 ng/mL) and cannabis had been used by the patient. No other recreational drugs were detected in an extensive toxicological screen of serum and urine samples. DISCUSSION: This is the first confirmed case to be reported of toxicity with delayed onset of severe agitation, hallucinations and tonic-clonic seizures associated with recreational use of Bromo-dragonFLY (1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane) in combination with ketamine and cannabis. In our view, this case provides further support for the need for a systematic approach to toxicological screening of patients with recreational drug toxicity, to identify emerging drugs and provide evidence for legislative authorities to assist in revising the legal status of emerging recreational drugs. (+info)
Degradation of 2-bromobenzoic acid by a strain of Pseudomonas aeruginosa.
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A strain of Pseudomonas aeruginosa producing 2-bromobenzoic acid, designated 2-BBZA, was isolated by enrichment culture from municipal sewage. It degraded all four 2-halobenzoates as well as certain 3-halo- and dihalobenzoates, though none of the 4-halobenzoates supported growth of this organism. 3-Hydroxybenzoate and 3-chlorocatechol were respective inhibitors of salicylate and catechol oxidation: when each was added separately to resting cells incubated with 2-bromobenzoate, salicylate and catechol were found. Oxygen uptake data suggest that the same dehalogenase may be involved in the oxidation of 2-bromo-, 2-chloro-, and 2-iodobenzoates. (+info)
Rodent thyroid, liver, and fetal testis toxicity of the monoester metabolite of bis-(2-ethylhexyl) tetrabromophthalate (tbph), a novel brominated flame retardant present in indoor dust.
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Enzymic determination of the free cholesterol fraction of high-density lipoprotein in plasma with use of 2,4,6-tribromo-3-hydroxybenzoic acid.
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A highly sensitive enzymic colorimetric reagent is described for determination of the free cholesterol fraction of high-density lipoprotein (HDL), which represents about 20% of the total cholesterol content of this lipoprotein. For greater sensitivity with respect to cholesterol, I used 2,4,6-tribromo-3-hydroxybenzoic acid instead of phenol in the cholesterol oxidase/peroxidase/4-aminoantipyrine reagent system. This allows determination of the free cholesterol fraction of HDL isolates prepared with polyethylene glycol 6000, a method for precipitating beta-lipoprotein that involves a twofold dilution of plasma. The reagent, adapted for use with a Cobas-Bio centrifugal analyzer, results in between-run and within-run CVs of less than 3% and a linearity to at least 400 mg of HDL free cholesterol per liter. Comparison with results by Trinder's cholesterol method, which measures cholest-4-en-3-one at 232 nm, showed good correlation (r = 0.9829, slope 1.0001, and y-intercept +2.4797 mg/L). With the manual procedure for HDL free cholesterol, between-batch and within-batch CVs were less than 5%, and results correlated well with those by the automated method (r = 0.9975, slope 0.9839, and y-intercept +2.4327 mg/L). The mean (and SD) HDL free cholesterol for 123 men was 96.8 (30.6) mg/L and for 122 women 136.4 (36.8) mg/L, indicating a distinct sex-related difference, similar to that found for HDL total cholesterol. HDL free cholesterol in plasma may therefore be a potential new predictor of coronary heart disease. (+info)
Reductive dechlorination of 2,4-dichlorobenzoate to 4-chlorobenzoate and hydrolytic dehalogenation of 4-chloro-, 4-bromo-, and 4-iodobenzoate by Alcaligenes denitrificans NTB-1.
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Alcaligenes denitrificans NTB-1, previously isolated on 4-chlorobenzoate, also utilized 4-bromo-, 4-iodo-, and 2,4-dichlorobenzoate but not 4-fluorobenzoate as a sole carbon and energy source. During growth, stoichiometric amounts of halide were released. Experiments with whole cells and cell extracts revealed that 4-bromo- and 4-iodobenzoate were metabolized like 4-chlorobenzoate, involving an initial hydrolytic dehalogenation yielding 4-hydroxybenzoate, which in turn was hydroxylated to 3,4-dihydroxybenzoate. The initial step in the metabolism of 2,4-dichlorobenzoate was catalyzed by a novel type of reaction for aerobic organisms, involving inducible reductive dechlorination to 4-chlorobenzoate. Under conditions of low and controlled oxygen concentrations, A. denitrificans NTB-1 converted all 4-halobenzoates and 2,4-dichlorobenzoate almost quantitatively to 4-hydroxybenzoate. (+info)