Day: November 16, 2022

Garay, R. P. published the artcileThe significance of the relative effects of loop diuretics and anti-brain edema agents on the sodium-potassium-chloride cotransport system and the chloride/NaCO3- anion exchanger, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is biol transport diuretic brain edema.

3-Amino-5-sulfamoylbenzoic acids and several series of (aryloxy)alkanoic acids were evaluated for their inhibitory effects on 2 human erythrocyte ion transport systems – the Na+,K+ cotransport system and the DIDS-sensitive anion carrier. Several classic loop diuretics, including the (aryloxy)alkanoic acid ethacrynic acid  [58-54-8] and several 3-amino-5-sulfamoylbenzoic acids, like bumetanide  [28395-03-1] and furosemide  [54-31-9], displayed relatively strong inhibitory activity vs. the cotransport system with relatively weaker action vs. the anion carrier. Furthermore, diuretic potency correlated with cotransport inhibitory potency. Another class of (aryloxy)alkanoic acids, namely the [(2,3-dihydro-1H-inden-5-yl)oxy]acetic acids, such as indacrinone  [56049-88-8] and MK-473  [53108-00-2], which exhibit less potent loop diuretic activity, were less potent cotransport inhibitors and more effective inhibitors of the anion carrier. Still other (aryloxy)alkanoic acids, with little saliuretic activity, namely a subclass of [(2,3-dihydro-1H-inden-5-yl)oxy]alkanoic acids and a series of [(2,3,9,9a-tetrahydro-1H-fluoren-7-yl)oxy]acetic acids displayed little or no inhibitory action on the cotransport system but enhanced inhibitory action on the anion carrier. The relative anion carrier inhibitory potency correlated well with the relative inhibitory activity of each compound on bicarbonate-stimulated cell swelling in cat cerebrocortical slices.

Naunyn-Schmiedeberg’s Archives of Pharmacology published new progress about Biological transport. 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Beaune, Ph. published the artcileImmunotoxicology and expression of human cytochrome P450 in microorganisms, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is autoimmune hepatitis drug cytochrome P450; microorganism human cytochrome P450 expression.

Drug-induced hepatitis can be caused by an abnormal immunol. response. In the case of tienilic acid- and dihydralazine-induced hepatitis, the authors postulated a scheme in which a P 450 produced a reactive metabolite (step 1); this reactive metabolite bound to the P 450 producing it (step 2) leading to a neoantigen triggering the immune response (step 3); the autoantibodies produced during the immune response recognized the P 450 producing the reactive metabolite (step 4). The use of microorganisms (yeast or bacteria) expressing cloned human P 450 helped in proving some steps of this postulated scheme, particularly steps 1 and 4.

Toxicology published new progress about Autoimmune hepatitis. 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, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Lopez-Garcia, M. Pilar published the artcileKinetics of tienilic acid bioactivation and functional generation of drug-protein adducts in intact rat hepatocytes, Category: benzothiophene, the main research area is tienilic acid bioactivation protein adduct hepatocyte.

Drug-induced autoimmune hepatitis is among the most severe hepatic idiosyncratic adverse drug reactions. Considered multifactorial, the disease combines immunol. and metabolic aspects, the latter being to date much better known. As for many other model drugs, studies on tienilic acid (TA)-induced hepatitis have evidenced the existence of bioactivation during the hepatic oxidation of the drug, allowing the identification of the neoantigen of anti-LKM2 autoantibodies and the pathway responsible for its formation. However, most of these results are based on the use of microsomal fractions whose relevance to the liver in vivo still needs to be established. In the more complex intact cell environment, several endogenous processes may play a significant role on triggering the reaction and should therefore be considered. In this work the authors have characterized the kinetics of TA biotransformation in metabolically competent hepatocytes, the influence of TA bioactivation on physiol. GSH levels, and the qual. and quant. profile of drug-protein conjugates generated in situ, as a function of exposure time. Results confirm that intact hepatocytes reproduce in vitro the metabolic sequence that leads to the functional generation of drug-protein adducts, in conditions that simulate clin. human exposure to TA. Metabolically competent cultured hepatocytes appear as a very promising approach to investigate the early preimmunol. events of drug-induced autoimmune hepatitis, adequate to identify the conditions that may modulate the formation and specificity of drug-protein adducts in vivo, to study the hepatic disposition of the TA-protein targets, and to define the specific role of the hepatocyte in the origin of this adverse reaction.

Biochemical Pharmacology published new progress about Autoimmune hepatitis. 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, Category: benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Dansette, P. M. published the artcileDrug-induced immunotoxicity, Application In Synthesis of 40180-04-9, the main research area is review drug immunotoxicity liver.

A review with 70 references is given on immune-response-related drug hepatitis. A number of organs may be the target of such reactions; however, this review concentrates mostly on the liver. Drug-induced hepatitis is generally divided into 2 categories: acute hepatitis in which the drug or a metabolite destroys a vital target in the cell; immunoallergic hepatitis in which the drug triggers an adverse immune response directed against the liver. Their clin. features are: (a) low frequency; (b) dose independence; (c) typical immune system manifestations such as fever, eosinophilia; (d) delay between the initiation of treatment and onset of the disease; (e) a shortened delay upon rechallenge; and (f) occasional presence of autoantibodies in the blood serum of patients. Such signs were found in cases of hepatitis triggered by drugs such as halothane, tienilic acid, dihydralazine, and anticonvulsants. They will be taken as examples to demonstrate the recent progress made in determining the mechanisms responsible for the disease. The following mechanisms were postulated. (1) The drug is 1st metabolized into a reactive metabolite which binds to the enzyme that generated it. (2) This produces a neo-antigen which, once presented to the immune system, might trigger an immune response characterized by (3) the production of antibodies recognizing both the native and/or the modified protein. (4) Rechallenge leads to increased neoantigen production, a situation in which the presence of antibodies may induce cytolysis. Toxicity is related to the nature and amount of neoantigen and also to other factors such as the individual immune system. An effort should be made to better understand the precise mechanisms underlying this kind of disease and thereby identify the drugs at risk; and also the neoantigen processes necessary for their introduction into the immune system. An animal model would be useful in this regard.

European Journal of Drug Metabolism and Pharmacokinetics published new progress about Autoimmune hepatitis. 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 In Synthesis of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Lecoeur, S. published the artcileTienilic acid-induced autoimmune hepatitis: anti-liver and -kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is autoimmune hepatitis tienilic acid cytochrome P4502C9.

Tienilic acid-induced hepatitis is characterized by the presence of anti-liver and -kidney microsomal (anti-LKM2) autoantibodies in patient sera. Cytochrome P 4502C9 (CYP2C9), involved in the metabolism of tienilic acid, was shown to be a target for tienilic acid-reactive metabolites and for autoantibodies. To further investigate the relationship between drug metabolism and the pathogenesis of this drug-induced autoimmune disease, the specificity of anti-LKM2 autoantibodies toward CYP2C9 was first determined, and the antigen sites on CYP2C9 were localized. By constructing several deletion mutants derived from CYP2C9 cDNA and by probing the corresponding proteins with different anti-LKM2 sera, we defined three regions (amino acids 314-322, 345-356, and 439-455); they interacted to form a major conformational autoantibody binding site. This binding site was immunoreactive with 100% of sera and allowed removal of the entire reactivity of the sera tested by immunoblotting. Epitope mapping studies have been performed for CYP2D6, CYP17, CYP21A2, and, recently, CYP3A. Those data were compared with the results obtained in the current study with CYP2C9 in an attempt to elucidate one of the mechanisms by which CYP becomes immunogenic.

Molecular Pharmacology published new progress about Autoimmune hepatitis. 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, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Vicente-Carrillo, A. published the artcileBoar spermatozoa successfully predict mitochondrial modes of toxicity: Implications for drug toxicity testing and the 3R principles, Related Products of benzothiophene, the main research area is boar sperm mitochondria toxicity drug testing; Boar; Drug; Mitochondria; Motility; Sperm; Toxicity.

Replacement of animal testing by in vitro methods (3-R principles) requires validation of suitable cell models, preferably obtained non-invasively, defying traditional use of explants. Ejaculated spermatozoa are highly dependent on mitochondrial production and consumption of ATP for their metabolism, including motility display, thus becoming a suitable model for capturing multiple modes of action of drugs and other chems. acting via mitochondrial disturbance. In this study, a hypothesis was tested that the boar spermatozoon is a suitable cell type for toxicity assessment, providing a protocol for 3R-replacement of animals for research and drug-testing. Boar sperm kinetics was challenged with a wide variety of known frank mito-toxic chems. with previously shown mitochondrial effects, using a semi-automated motility analyzer allied with real-time fluorescent probing of mitochondrial potential (MitoTracker & JC-1). Output of this sperm assay (obtained after 30 min) was compared to cell viability (ATP-content, data obtained after 24-48 h) of a hepatome-cell line (HepG2). Results of compound effects significantly correlated for all sperm variables and for most variables in (HepG2). Dose-dependent decreases of relative ATP content in HepG2 cells correlated to sperm speed (r = 0.559) and proportions of motile (r = 0.55) or progressively motile (r = 0.53) spermatozoa. The significance of the study relies on the objectivity of computerized testing of sperm motility inhibition which is comparable albeit of faster output than somatic cell culture models. Sperm suspensions, easily and painlessly obtained from breeding boars, are confirmed as suitable biosensors for preclin. toxicol. screening and ranking of lead compounds in the drug development processes.

Toxicology In Vitro published new progress about Antimicrobial agents. 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

Murcia-Soler, Miguel published the artcileDiscrimination and selection of new potential antibacterial compounds using simple topological descriptors, Product Details of C13H8Cl2O4S, the main research area is antibacterial topol structure activity relationship.

The aim of the work was to discriminate between antibacterial and non-antibacterial drugs by topol. methods and to select new potential antibacterial agents from among new structures. The method used for antibacterial activity selection was a linear discriminant anal. (LDA). It is possible to obtain a QSAR interpretation of the information contained in the discriminant function. We make use of the pharmacol. distribution diagrams (PDDs) as a visualizing technique for the identification and selection of new antibacterial agents.

Journal of Molecular Graphics & Modelling published new progress about Antibacterial agents. 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

Pacitto, Stephanie R. published the artcileChanges in gene expression induced by tienilic acid and sulfamethoxazole: testing the danger hypothesis, HPLC of Formula: 40180-04-9, the main research area is tienilic acid sulfamethoxazole gene expression microarray idiosyncratic drug toxicity; cell stress tienilate sulfamethoxazole idiosyncratic drug toxicity.

Tienilic acid (TA) was withdrawn due to idiosyncratic hepatotoxicity. Two hypotheses for the mechanisms of idiosyncratic reactions are the hapten and danger hypotheses, which are not mutually exclusive. Both human CYP 2C9 and rat CYP 2C11 metabolize TA to a reactive metabolite that was reported to bind exclusively to these enzymes. TA-Induced liver toxicity is associated with antibodies against CYP 2C9, thus TA appears to act as a hapten. However, if the binding were limited to CYP 2C, it is unlikely that this would lead to significant cell stress. If TA does not cause cell stress it would suggest that acting as a hapten is sufficient to induce an idiosyncratic reaction. To test whether TA can cause cell stress rats were dosed with TA and hepatic gene expression was profiled at 6 and 24 h after drug administration. TA induced changes in genes involved in oxidative stress (aldo-keto reductase, glutathione-S-transferase, thioredoxin reductase, epoxide hydrolase), inflammation (IL-1β, interferon regulatory factor 1, macrophage stimulating protein 1), cytotoxicity (caspase-12), and liver regeneration (p27Kip1, DUSP6, serine dehydratase, spectrin βII, inhibin βA). These data support the hypothesis that danger signals in the form of cell-stress may be involved in initiating the immune response observed in TA-induced toxicity. In sep. experiments, the authors examined the changes in gene expression induced in mice by sulfamethoxazole, which also causes idiosyncratic reactions. Sulfamethoxazole is an aromatic amine, and aromatic amines in general are associated with idiosyncratic drug reactions. They form reactive metabolites that both act as electrophiles and can redox cycle; therefore, it was assumed that sulfamethoxazole would cause some type of cell stress, the only question was what changes in mRNA expression would occur. In contrast to expectations, no changes induced by sulfamethoxazole could easily be interpreted as a danger signal. These data are presented together because they are the opposite of the expected results and convey a complex story.

Journal of Immunotoxicology published new progress about Antibacterial agents. 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

Tighadouini, Said published the artcileSynthesis, Biochemical Characterization, and Theoretical Studies of Novel β-Keto-enol Pyridine and Furan Derivatives as Potent Antifungal Agents, Synthetic Route of 1468-83-3, the main research area is keto enol pyridine furan antifungal antibacterial mol docking dynamic.

In the present study, we report the design and synthesis of new derivatives of the β-keto-enol grafted on pyridine and furan moieties (L1-L11). Structures of compounds were fully confirmed by Fourier transform IR spectroscopy (FT-IR), 1H NMR, 13C NMR, electrospray ionization/liquid chromatog.-mass spectrometry (ESI/LC-MS), and elemental anal. The compounds were screened for antifungal and antibacterial activities (Escherichia coli, Bacillus subtilis, and Micrococcus luteus). In vitro evaluation showed significant fungicidal activity for I, II, and III against fungal strains (Fusarium oxysporum f.sp albedinis) compared to the reference standard Especially, the exceptional activity has been demonstrated for I with IC50 = 12.83μg/mL. This compound and the reference benomyl mol. also showed a correlation between exptl. antifungal activity and theor. predictions by Petra/Osiris/Molinspiration (POM) calculations and mol. coupling against the Fgb1 protein. The highest inhibition of bacterial growth for I is due to its strongest binding to the target protein. This report may stimulate the further synthesis of examples of this substance class for the development of new drugs.

ACS Omega published new progress about Antibacterial agents. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Synthetic Route of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Tighadouini, Said published the artcileNovel β-keto-enol Pyrazolic Compounds as Potent Antifungal Agents. Design, Synthesis, Crystal Structure, DFT, Homology Modeling, and Docking Studies, Synthetic Route of 1468-83-3, the main research area is antibacterial antifungal crystal structure mol docking pharmacol SAR DFT; keto enol pyrazole derivative preparation.

A new family of promising inhibitors bearing β-keto-enol functionality with greatly improved pharmacophore properties has been prepared Herein, a series of novel derivatives of β-keto-enol group embedded with pyrazolic moiety has been designed and synthesized via a one-step procedure using mixed Claisen condensation in the attempt to develop potential antifungal agents. The structures of the synthesized compounds were confirmed by elemental anal., FT-IR, ESI/LC-MS, and 1H and 13C NMR. In addition, X-ray diffraction anal. (XRD) was used to determine the single crystal structure of compound I. All of the new compounds have been evaluated for their in vitro antifungal and antibacterial activities. Interestingly, the results indicate that most of the compounds display notable antifungal activity close to that of the benomyl fungicide taken as the standard drug. For the most active compound and for benomyl, a correlation has been evidenced between the exptl. antifungal activity and the theor. predictions by DFT calculations and mol. docking against Fgb1 protein.

Journal of Chemical Information and Modeling published new progress about Antibacterial agents. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Synthetic Route of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem