Day: November 18, 2022

Dansette, P. M. published the artcileOxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is thiophene metabolism liver monooxygenase cytochrome; tienilic acid metabolism liver cytochrome P450.

Tienilic acid (TA) is metabolized by liver microsomes from phenobarbital-treated rats in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the regioselective hydroxylation of the thiophene ring of TA. During this in vitro metabolism of TA, reactive electrophilic intermediates which bind irreversibly to microsomal proteins are formed. 5-Hydroxylation of TA and activation of TA to reactive metabolites which covalently bind to proteins required intact microsomes, NADPH and O and are inhibited by metyrapone and SKF 525A, indicating that they are dependent on monooxygenases using cytochromes P 450. Microsomal oxidation of an isomer of TA (TAI) bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring also leads to reactive intermediates able to bind covalently to microsomal proteins. Covalent binding of TAI, as that of TA, depends on cytochrome P 450-dependent monooxygenases and is almost completely inhibited in the presence of S-containing nucleophiles such as glutathione, cysteine or cyteamine. These results show that 5-OHTA, which has been reported as the major metabolite of TA in vivo in humans, is formed by liver microsomes by a cytochrome P 450-dependent reaction. They also show that 2 thiophene derivatives, TA and TAI, bind to microsomal proteins after in vitro metabolic activation, TAI giving a much higher level of covalent binding than TA (about 5-fold higher) and a much higher covalent binding:stable metabolites ratio (4 instead of 0.5).

Biochemical Pharmacology published new progress about Liver. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ayotte, P. published the artcileFailure of phenobarbital or butanediol pretreatment to potentiate tienilic acid hepatotoxicity in vivo in the rat, Product Details of C13H8Cl2O4S, the main research area is tienilate liver toxicity phenobarbital butanediol.

Tienilic acid  [40180-04-9], a uricosuric diuretic, has been associated with hepatocellular injury in humans as a low-incidence adverse reaction. This phenomenon suggests that a metabolic idiosyncrasy may be involved. The effect of phenobarbital  [50-06-6] and 1,3-butanediol  [107-88-0] pretreatment, prior to tienilic acid challenge (50 or 100 mg/kg, i.v.) on rat hepatic function was studied in vivo. The following parameters were assessed: plasma alanine aminotransferase activity, plasma bilirubin concentration, and bile flow. The results show that neither pretreatment would reveal that tienilic acid possesses hepatotoxic properties in the rat. The discrepancies between these results observed in vivo and those obtained by others in the isolated perfused rat liver suggest: a) that a metabolite formed (under normal conditions) via the phenobarbital- or butanediol-inducible forms of cytochrome P 450  [9035-51-2] is not a likely part of the hepatotoxic sequence of events; b) that the isolated perfused rat liver model in this case is not representative of the in vivo situation.

Archives Internationales de Pharmacodynamie et de Therapie published new progress about Liver. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Product Details of C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Hildebrandt, E. published the artcileIndirect inhibition of vitamin K epoxide reduction by salicylate, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is salicylate vitamin K epoxide reductase.

Salicylate  [69-72-7] antagonizes the vitamin K  [12001-79-5]-dependent biosynthesis of clotting factors in the rat and produces an elevation of the ratio of vitamin K epoxide  [25486-55-9] to vitamin K in the liver. Vitamin K epoxide is reduced to vitamin k by a vitamin K epoxide reductase  [55963-40-1], and 1 mM salicylate was required to cause a 50% inhibition of the dithiothreitol-dependent in-vitro reduction of vitamin K epoxide by this enzyme. This enzyme was, however, inhibited 50% by as little as 70-80 μM salicylate when reducing equivalent for the reaction were furnished by endogenous cytosolic reductants. This effect on the cytosolic reductant supply was shown to be unrelated to a previously demonstrated inhibition of DT-diaphorase by salicylate. The concentrations of salicylate at which significant inhibitory effects are exerted are in-vitro (50-100 μM) are below the 200 μM levels observed in the livers of rats given an anticoagulating dose of salicylate.

Journal of Pharmacy and Pharmacology published new progress about Liver. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Acosta, Daniel published the artcileLack of cytotoxicity of ticrynafen in primary cultures of rat liver cells, HPLC of Formula: 40180-04-9, the main research area is tricrynafen cytotoxicity liver.

Primary cultures of hepatocytes obtained from neonatal Sprague-Dawley rats were grown in arginine-deficient, ornithine-supplemented medium to inhibit fibroblastic overgrowth and to selectively isolate relatively pure cultures of parenchymal hepatocytes. This system of primary hepatocytes was used to study the potential cytotoxicity of ticrynafen (I) [40180-04-9] by measuring cytoplasmic enzyme leakage, cell viability, and total protein per culture dish. Hepatic cultures were treated with the drug in concentrations ranging from 10-3 M to 10-6 M and for durations from 2 to 8 h. The results of the study indicate that ticrynafen was minimally toxic to the hepatocytes.

Toxicology Letters published new progress about Liver. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, HPLC of Formula: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ahmed, Nahed K. published the artcileComparison and characterization of mammalian xenobiotic ketone reductases, Quality Control of 40180-04-9, the main research area is drug metabolism ketone reductase enzyme; liver kidney ketone drug reduction.

Rabbit liver extracts catalyzed the reduction of the ketone group of the following drugs: oxisuran [27302-90-5], metyrapone [54-36-4], naloxone [465-65-6], naltrexone [16590-41-3], 3,7-dimethyl-1-(5-oxohexyl)-xanthine (3,7-DMX) [6493-05-6], and daunorubicin [20830-81-3]. The reductases catalyzing these reactions were extracted from rabbit liver and characterized. Significant activity was also extracted from human liver, but rat and mouse livers had very low levels of the ketone reductases. Although reductase activity occurs mainly in the liver and kidney, detectable activity was also observed in spleen, lung, and brain. All drug reductases displayed an acid pH optimum, had an absolute requirement for NADPH as cofactor, and occurred primarily as cytoplasmic enzymes. Although the reductases elute from gel filtration chromatog. in slightly different volumes, all enzymes have mol. weights in the range of 32,000 to 38,000 daltons. The drug reductases were not significantly inhibited by phenobarbital or by pyrazole, suggesting that the ketone reductases exist as a class of enzymes distinct from aromatic aldehyde reductases and classical alc. dehydrogenase. The ketone reductases were inhibited by the plant flavonoid quercitrin. Isoelec. focusing resolved drug reductases into multiple forms. The major activities for 3,7-DMX, oxisuran, and metyrapone focused as a single sym. coincident peak with a pI of 4.8, whereas the majority of naloxone and naltrexone reductases focused as heterogeneous bands above pH 6.0. Minor forms of most of the drug reductases were also evident.

Journal of Pharmacology and Experimental Therapeutics published new progress about Brain. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Quality Control of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Oker-Blom, Christian published the artcileToxicological studies on tienilic acid in rats, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilic acid toxicity; sex tienilic acid toxicity.

The subacute oral toxicity of tienilic acid (I) [40180-04-9] in male and female rats was studied. Animals were given 0, 30, 120, and 480 mg I/kg as a 3% gum arabic suspension for 28 days. At 30 mg I/kg, blood pressure and serum uric acid [69-93-2] decreased. At the 2 higher dose levels, a slight decrease in Hb and an increase in serum glutamic-pyruvic transaminase [9000-86-6] activity was noticed, and there was a significant increase in the liver weight and serum Mg concentration of male rats, while the liver weight of female rats increased only slightly. One microscopic examination, unicellular necrosis of small groups of liver cells was noted, together with focal round-cell infiltration and some stasis of the 2 higher dose levels in some animals. I had no noticeable effects on other organs or parameters.

Toxicology Letters published new progress about Blood. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Lemieux, G. published the artcileThe renal handling of tienilic acid (ticrynafen), a new diuretic with uricosuric properties, HPLC of Formula: 40180-04-9, the main research area is tienilic acid diuresis kidney; ticrynafen diuresis mechanism.

Tienilic acid (I) [40180-04-9] was highly bound to plasma proteins of dogs at 37° (>95% at drug concentrations of 3.0-20.0 mg/dL). Thus, glomerular filtration of the drug is negligible and I must reach the kidney at the antiluminal site of the tubule. During free-flow studies, the clearance of I at stable plasma concentrations (3.0-20.0 mg/dL) ranged from 11-22% of glomerular filtration. These values are 3-5 times greater than that accounted for by filtration of the drug alone and are highly suggestive of tubular secretion. Secretion becomes more apparent during alkalinization of the urine when the clearance of I may rise to 40 and even 100% of glomerular filtration. During stop-flow studies, the urine over plasma ratio of the drug (U/P TA) over that of creatinine (U/P Cr) decreased along the nephron indicating progressive reabsorption. At equivalent plasma concentration, I markedly depressed p-aminohippuric acid (PHA) transport in the proximal tubule. When plasma I concentration was kept low (5 mg/dL) and PAH concentration was raised to 30 mg/dL, the (U/P TA)/(U/P Cr) dropped by 50%. These results indicate active secretion of I in the proximal tubule followed by passive pH dependent reabsorption along the nephron. The drug is transported through the common organic acid pathway by a carrier having higher affinity for I than for PAH.

Nephron published new progress about Kidney. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, HPLC of Formula: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ullrich, Karl J. published the artcileContraluminal organic anion and cation transport in the proximal renal tubule: V. Interaction with sulfamoyl- and phenoxy diuretics, and with β-lactam antibiotics, SDS of cas: 40180-04-9, the main research area is kidney tubule contraluminal ion transport; xenobiotic ion transport kidney tubule; antibiotic ion transport kidney tubule; diuretic ion transport kidney tubule.

In order to study the interaction of sulfamoyl- and phenoxy-diuretics as well as of β-lactam antibiotics with the contraluminal anion and cation transport systems, the inhibitory potency of these substances against the influx of [3H]p-aminohippurate, [14C]succinate, [35S]sulfate, and [3H]N1-methylnicotinamide into cortical tubular cells were determined The results show that the probenecid, the diuretics furosemide, piretanide, hydrochlorothiazide, acetazolamide, ethacrynic, and tielinic acid, and the β-lactam antibiotics of the penicillin and cephalosporin type interact with the anion and cation transport systems in a predictable fashion.

Kidney International published new progress about Anions. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, SDS of cas: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Dan, Takashi published the artcileUricosurics inhibit urate transporter in rat renal brush border membrane vesicles, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is uricosuric urate transporter kidney brush border.

It has been proposed that a urate-anion exchanger system in brush border membrane vesicles (BBMV), which mediates hydroxyl ion (OH-) gradient-dependent urate uptake, is the most likely route for the mediation of urate transport in the first step of urate reabsorption in the proximal tubules. Luminal drugs which inhibit urate reabsorption would inhibit the transport of urate into the cell by blocking the urate-anion exchanger. To confirm this hypothesis, the inhibitory effects of well-known uricosuric drugs on the OH-/urate exchange in BBMV were studied. The rank order of potency was benzbromarone > tienilic acid > sulfinpyrazone > probenecid, which is consistent with clin. doses in man. AA-193 (5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carboxylic acid), an excellent candidate for a uricosuric, exerted the most potent inhibition on urate uptake (Ki = 0.12 μM). In contrast with that by stilbene disulfonates, the inhibition by AA-193 or benzbromarone was reversible.

European Journal of Pharmacology published new progress about Anions. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ahokas, J. T. published the artcileThe effect of tienilic acid on paracetamol toxicity, Related Products of benzothiophene, the main research area is tienilate paracetamol toxicity glutathione transferase.

Tienilic acid (I) [40180-04-9] inhibited the activity of mouse liver cytosolic glutathione-S-transferase (GSH-t) [50812-37-8] in vitro, with inhibition ranging 23-48%. In mice, the administration of paracetamol (II) [103-90-2] (302 mg/kg, i.p.), a drug normally detoxified through conjugation by the GSH-t system, along with I (40 mg/kg, i.p.) did not result in an increase of II toxicity. Thus, the interaction between II and a strong GSH-t inhibitor, I, does not lead to enhanced II toxicity. Results are discussed with respect to II detoxification via GSH-t.

IRCS Medical Science published new progress about Cytosol. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem