Month: November 2022

Wright, Kirsten M. published the artcileCentella asiatica water extract shows low potential for cytochrome P450-mediated drug interactions, Related Products of benzothiophene, the main research area is Centella asiatica water extract cytochromeP drug interaction.

Centella asiatica (CA) shows considerable promise for development as a botanical drug for cognitive decline. Its primary bioactive components include triterpene glycosides asiaticoside and madecassoside and their corresponding aglycons asiatic acid and madecassic acid. Exploration of the bioactivity of CA’s caffeoylquinic acids is ongoing. In this study, an aqueous extract of CA (CAW-R61J) was evaluated for drug interaction potential through inhibition or induction of P 450 enzymes, as required by the US Food and Drug Administration. CAW-R61J was assessed for induction potential of CYP1A2, CYP2B6, and CYP3A4 using transporter-certified cryopreserved human hepatocytes in sandwich culture. Gene expression of these target P450s was quantified, and enzyme activities were determined to confirm gene expression results. No induction was observed up to 16.7μg/mL CAW-R61J (equivalent to 1.1μM asiaticoside, 0.8μM madecassoside, 0.09μM asiatic acid, and 0.12μM madecassic acid). Reversible and time-dependent inhibitory effects of CAW-R61J on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 were evaluated using human liver microsomes. CAW-R61J showed weak reversible inhibition of most of the P 450 forms tested, with the strongest being CYP2C9 (IC50 of 330μg/mL). CAW-R61J (â‰?000μg/mL) was not a time-dependent inhibitor of any of these P 450 enzymes. In summary, CAW-R61J had no, or only a weak impact, on P 450 induction and inhibition in vitro. The clin. relevance of these results will depend on the in vivo concentration of CAW-R61J components achieved in humans. Plasma triterpene concentrations measured in our recent clin. studies suggest minimal risk of P 450-mediated drug interactions by these components.

Drug Metabolism & Disposition published new progress about Aglycons Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Geng, Xiao published the artcileI2-Promoted Multicomponent Dicyclization and Ring-Opening Sequences: Direct Synthesis of Benzo[e][1,4]diazepin-3-ones via Dual C-O Bond Cleavage, SDS of cas: 1468-83-3, the main research area is ketone aryl methyl aminobenzyl alc DMSO iodine dicyclization ringopening; benzodiazepinone preparation.

A novel and efficient formal [4 + 2+1] annulation of aryl Me ketones and 2-aminobenzyl alcs. for the synthesis of benzo[e][1,4]diazepin-3-ones I (Ar = Ph, 4-MeOC6H4, 4-PhC6H4, 3-NO2C6H4, etc.; R = 7-Me, 7-F, 8-Me, etc.) is reported. This reaction successfully affords diverse seven-membered ring lactams via dual C-O bond cleavage. A preliminary mechanistic study showed that a multicomponent dicyclization and ring-opening sequence might occur, with the introduction of Me sulfide proposed as the last step. This efficient strategy with mild reaction conditions and a broad substrate scope has potential applications in chem. and medicine.

Organic Letters published new progress about Alkyl aryl ketones Role: RCT (Reactant), RACT (Reactant or Reagent) (aryl Me). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, SDS of cas: 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

McDonald, Matthew G. published the artcileModulation of major human liver microsomal cytochromes P450 by component alkaloids of goldenseal: time-dependent inhibition and allosteric effects, Synthetic Route of 40180-04-9, the main research area is human liver microsomal cytochrome alkaloid goldenseal allosteric effect.

Botanical and other natural products (NPs) are often coconsumed with prescription medications, presenting a risk for cytochrome P 450 (P 450)-mediated NP-drug interactions. The NP goldenseal (Hydrastis canadensis) has exhibited antimicrobial activities in vitro attributed to isoquinoline alkaloids contained in the plant, primarily berberine, (-)-β hydrastine, and to a lesser extent, hydrastinine. These alkaloids contain methylenedioxyphenyl rings, structural alerts with potential to inactivate P450s through formation of metabolic intermediate complexes. Time-dependent inhibition experiments were conducted to evaluate their ability to inhibit major P 450 activities in human liver microsomes by using a cocktail of isoenzyme-specific substrate probes. Berberine inhibited CYP2D6 (dextromethorphan O-demethylation; KI = 2.7μM, kinact = 0.065 min-1) and CYP3A4/5 (midazolam 1′-hydroxylation; KI = 14.8μM, kinact = 0.019 min-1); (-)-β-hydrastine inhibited CYP2C9 (diclofenac 4′-hydroxylation; KI = 49 ηM, kinact = 0.036 min-1), CYP2D6 (KI > 250μM, kinact > 0.06 min-1), and CYP3A4/5 (KI = 28μM, kinact = 0.056 min-1); and hydrastinine inhibited CYP2D6 (KI = 37μM, kinact = 0.049 min-1) activity. Berberine addnl. exhibited allosteric effects on midazolam hydroxylation, showing both pos. and neg. heterotropic cooperativity. Experiments with recombinant isoenzymes showed that berberine activated midazolam 1′-hydroxylation by CYP3A5, lowering Km(app), but showed mixed inhibition and neg. cooperativity toward this reaction when catalyzed by CYP3A4. Berberine inactivated CYP3A4 at a much faster rate than CYP3A5 and was a noncompetitive inhibitor of midazolam 4-hydroxylation by CYP3A4 but a strong mixed inhibitor of the CYP3A5 catalyzed reaction. These complex kinetics should be considered when extrapolating the risk for NP-drug interactions involving goldenseal. Robust kinetic parameters were determined for the reversible and timedependent inhibition of CYP2C9, CYP2D6, and CYP3A4/5 activities in human liver microsomes by major component isoquinoline alkaloids contained in the botanical natural product goldenseal. The alkaloid berberine also exhibited opposing, isoenzyme-specific allosteric effects on midazolam hydroxylation mediated by recombinant CYP3A4 (inhibition) and CYP3A5 (activation). These data will inform the development of a physiol. based pharmacokinetic model that can be used to predict potential clin. relevant goldenseal-drug interactions.

Drug Metabolism & Disposition published new progress about Alkaloids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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, Synthetic Route of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Nishiya, Takayoshi published the artcileThe crucial protective role of glutathione against tienilic acid hepatotoxicity in rats, Application In Synthesis of 40180-04-9, the main research area is glutathione tienilic acid hepatotoxicity.

To investigate the hepatotoxic potential of tienilic acid in vivo, the authors administered a single oral dose of tienilic acid to Sprague-Dawley rats and performed general clinicopathol. examinations and hepatic gene expression anal. using Affymetrix microarrays. No change in the serum transaminases was noted at up to 1000 mg/kg, although slight elevation of the serum bile acid and bilirubin, and very mild hepatotoxic changes in morphol. were observed In contrast to the marginal clinicopathol. changes, marked upregulation of the genes involved in glutathione biosynthesis [glutathione synthetase and glutamate-cysteine ligase (Gcl)], oxidative stress response [heme oxygenase-1 and NAD(P)H dehydrogenase quinone 1], and phase II drug metabolism (glutathione S-transferase and UDP glycosyltransferase 1A6) were noted after 3 or 6 h postdosing. The hepatic reduced glutathione level decreased at 3-6 h, and then increased at 24 or 48 h, indicating that the upregulation of NF-E2-related factor 2 (Nrf2)-regulated gene and the late increase in hepatic glutathione are protective responses against the oxidative and(or) electrophilic stresses caused by tienilic acid. In a subsequent experiment, tienilic acid in combination with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of Gcl, caused marked elevation of serum alanine aminotransferase (ALT) with extensive centrilobular hepatocyte necrosis, whereas BSO alone showed no hepatotoxicity. The elevation of ALT by this combination was observed at the same dose levels of tienilic acid as the upregulation of the Nrf2-regulated genes by tienilic acid alone. Apparently, the impairment of glutathione biosynthesis may play a critical role in the development of tienilic acid hepatotoxicity through extensive oxidative and(or) electrophilic stresses.

Toxicology and Applied Pharmacology published new progress about Bile acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Gong, Eun Chae published the artcileEnzyme kinetics and molecular docking studies on cytochrome 2B6, 2C19, 2E1, and 3A4 activities by sauchinone, Application In Synthesis of 40180-04-9, the main research area is liver microsome sauchinone cytochrome mol docking enzyme kinetics; CYP450; Saururus chinensis; docking; herb-drug interaction; human liver microsome; metabolic inhibition; sauchinone.

Sauchinone, an active lignan isolated from the aerial parts of Saururus chinensis (Saururaceae), exhibits anti-inflammatory, anti-obesity, anti-hyperglycemic, and anti-hepatic steatosis effects. As herb-drug interaction (HDI) through cytochrome P450s (CYPs)-mediated metabolism limits clin. application of herbs and drugs in combination, this study sought to explore the enzyme kinetics of sauchinone towards CYP inhibition in in vitro human liver microsomes (HLMs) and in vivo mice studies and computational mol. docking anal. In in vitro HLMs, sauchinone reversibly inhibited CYP2B6, 2C19, 2E1, and 3A4 activities in non-competitive modes, showing inhibition constant (Ki) values of 14.3, 16.8, 41.7, and 6.84μM, resp. Also, sauchinone time-dependently inhibited CYP2B6, 2E1 and 3A4 activities in vitro HLMs. Mol. docking study showed that sauchinone could be bound to a few key amino acid residues in the active site of CYP2B6, 2C19, 2E1, and 3A4. When sibutramine, clopidogrel, or chlorzoxazone was co-administered with sauchinone to mice, the systemic exposure of each drug was increased compared to that without sauchinone, because sauchinone reduced the metabolic clearance of each drug. In conclusion, when sauchinone was co-treated with drugs metabolized via CYP2B6, 2C19, 2E1, or 3A4, sauchinone-drug interactions occurred because sauchinone inhibited the CYP-mediated metabolic activities.

Molecules published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Zhang, Linli published the artcileLutidine-Based Chiral Pincer Manganese Catalysts for Enantioselective Hydrogenation of Ketones, COA of Formula: C6H6OS, the main research area is alc preparation enantioselective; ketone hydrogenation manganese catalyst; PNN ligands; asymmetric catalysis; hydrogenation; ketones; manganese.

A series of MnI complexes containing lutidine-based chiral pincer ligands (S,S) or (R,R) I (R = H, Me, t-Bu, Cl, OMe; R1 = i-Pr, Bn) with modular and tunable structures has been developed. The complex shows unprecedentedly high activities (up to 9800 TON; TON = turnover number), broad substrate scope (81 examples), good functional-group tolerance, and excellent enantioselectivities (85-98% ee) in the hydrogenation of various ketones, e.g., acetophenone. These aspects are rare in earth-abundant metal catalyzed hydrogenations. The utility of the protocol have been demonstrated in the asym. synthesis of a variety of key intermediates for chiral drugs. Preliminary mechanistic investigations indicate that an outer-sphere mode of substrate-catalyst interactions probably dominates the catalysis.

Angewandte Chemie, International Edition published new progress about Alcohols Role: PRP (Properties), SPN (Synthetic Preparation), PREP (Preparation). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, COA of Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Zhong, Rui published the artcileA Practical and Stereoselective In Situ NHC-Cobalt Catalytic System for Hydrogenation of Ketones and Aldehydes, Formula: C6H6OS, the main research area is cobalt complex catalyst preparation; secondary alc primary preparation diastereoselective; ketone hydrogenation cobalt catalyst; aldehyde hydrogenation cobalt catalyst.

Herein, a practical in situ catalytic system generated by easily available pincer NHC precursors, CoCl2 and a base enabled efficient and high-yielding hydrogenation of a broad range of ketones and aldehydes (over 50 examples and a maximum turnover number [TON] of 2,610) to afford alcs. was reported. This was the first example of NHC-Co-catalyzed hydrogenation of C=O bonds using flexible pincer NHC ligands consisting of a N-H substructure. Diastereodivergent hydrogenation of substituted cyclohexanone derivatives was also realized by fine-tuning of the steric bulk of pincer NHC ligands. Addnl., a bis(NHCs)-Co complex was successfully isolated and fully characterized and it exhibited excellent catalytic activity that equals that of the in-situ-formed catalytic system.

Chem published new progress about Alcohols Role: PRP (Properties), SPN (Synthetic Preparation), PREP (Preparation). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Robin, Marie-Anne published the artcileAntigenic targets in tienilic acid hepatitis. Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and recognized by human sera, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is neoantigen tienilate cytochrome P 450 hepatitis.

Patients with tienilic acid hepatitis exhibit autoantibodies that recognize unalkylated cytochrome P 450 2C9 in humans but recognize 2C11 in rats. The aim of this study was to determine whether the immune reaction is also directed against neoantigens. Rats were treated with tienilic acid and hepatocytes were isolated. Immunoprecipitation, immunoblotting, and flow cytometry experiments were performed with an anti-tienilic acid or an anti-cytochrome P 450 2C11 antibody. Cytochrome P 450 2C11 was the main microsomal or plasma membrane protein that was alkylated by tienilic acid. Inhibitors of vesicular transport decreased flow cytometric recognition of both unalkylated and tienilic acid-alkylated cytochrome P 450 2C11 on the plasma membrane of cultured hepatocytes. Tienilic acid hepatitis sera that were preadsorbed on microsomes from untreated rats (to remove autoantibodies), poorly recognized untreated hepatocytes in flow cytometry experiments, but better recognized tienilic acid-treated hepatocytes. This recognition was decreased by adsorption with tienilic acid or by pre-exposure to the anti-tienilic acid or the anti-cytochrome P 450 2C11 antibody. The authors conclude that cytochrome P 450 2C11 is alkylated by tienilic acid and follows a vesicular route to the plasma membrane. Tienilic acid hepatitis sera contain antibodies against this tienilic acid adduct, in addition to the previously described anti-cytochrome P 450 autoantibodies.

Journal of Clinical Investigation published new progress about Autoantibodies Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Manns, Michael P. published the artcileRecent developments in autoimmune liver diseases, Category: benzothiophene, the main research area is review autoimmune liver disease.

A review with 141 references Several diseases are regarded as autoimmune liver diseases. Apart from the cholestatic liver diseases, primary biliary cirrhosis, primary sclerosing cholangitis, these include autoimmune hepatitis, hepatitis as part of the autoimmune polyendocrine syndrome type 1 (APS-1) and particular overlap syndromes such as autoimmune cholangitis (also called anti-mitochondrial antibody neg. primary biliary cirrhosis [PBC]), overlap syndrome chronic active hepatitis (CAH)/PBC and the overlap syndrome primary sclerosing hepatitis (PSC)/CAH. In addition, auto-antibodies may be observed during the course of chronic viral hepatitis, in particular chronic hepatitis C and D. Finally, a small number of drug-induced liver diseases is immune mediated. The author also discusses recent progress in the field of autoimmune hepatitis including APS-1 and autoimmunity in viral hepatitis and immune-mediated drug-induced liver disease.

Journal of Gastroenterology and Hepatology published new progress about Autoantibodies Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Liu, Yitong published the artcileAnthraquinones inhibit cytochromes P450 enzyme activity in silico and in vitro, COA of Formula: C13H8Cl2O4S, the main research area is anthraquinone cytochrome enzyme activity human liver microsome; QSAR; aloe-emodin; anthraquinone; cytochrome P450 enzyme; emodin; human liver microsome; human recombinant enzyme; inhibition; rhein.

Anthraquinones exhibit various pharmacol. activities (e.g., antioxidant and laxative) and are commonly found in consumer products including foods, dietary supplements, drugs, and traditional medicines. Despite their widespread use, there are limited data available on their toxicokinetic properties. Cytochrome P 450 enzymes (CYPs) in the liver play major roles in metabolizing exogenous chems. (e.g., pharmaceuticals, food ingredients, and environmental pollutants) and endogenous biomols. (e.g., steroid hormones and cholesterol). Inhibition of CYP activities may lead to serious interactions among these compounds Here, in silico (quant. structure-activity relationship modeling) and in vitro (human recombinant enzymes and liver microsomes) methods were used to identify inhibitors of five major CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) among 22 anthraquinones. First, in silico prediction and in vitro human recombinant enzyme assays were conducted for all compounds, and results showed that most of the anthraquinones were potent CYP1A2 inhibitors. Second, five selected anthraquinones (emodin, aloe-emodin, rhein, purpurin, and rubiadin) were further evaluated in human liver microsomes. Finally, plasma concentrations of the five anthraquinones in animal and humans were identified in the literature and compared to their in vitro inhibition potency (IC50 values) towards CYP activities. Emodin, rhein, and aloe-emodin inhibited activities of multiple CYPs in human liver microsomes and potential in vivo inhibition may occur due to their high plasma concentrations These in silico and in vitro results enabled rapid identification of potential CYP inhibitors and prioritized future in-depth studies.

Journal of Applied Toxicology published new progress about Anthraquinones Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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, COA of Formula: C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem