Day: November 16, 2022

Mersch-Sundermann, Volker published the artcileSOS induction in Escherichia coli and Salmonella mutagenicity: a comparison using 330 compounds, SDS of cas: 40180-04-9, the main research area is SOS induction Escherichia Salmonella mutagenicity.

To examine the concordance of two microbial genotoxicity short-term assays, 330 exptl. results for the SOS chromotest using tester strain Escherichia coli PQ37 were compared with the results of the Salmonella/mammalian microsome mutagenicity assay with Salmonella typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and/or TA1538. With respect to qual. features, the concordance between SOS chromotest and Salmonella mutagenicity test results was 86.4% (sensitivity, 78.6%; specificity, 100%; χ2 = 188.6). None of the non-mutagens (N = 120) were able to induce the SOS system. Addnl., 45 of the 210 S. typhimurium mutagens (21.5%) did not induce the SOS repair system. On closer examination, the majority of these 45 compounds (84%) were mutagens with activities between 0.001 and 10 rev/nmol. Even though the exptl. protocols of both systems were not standardized, the correlation coefficient for the exptl. results of the two test systems was 0.7 for the 330 chems. Except for aliphatic epoxides (r = 0.47), the mutagenicity/SOS induction correlations for congeneric data sets (polycyclic aromatic hydrocarbons, nitroarenes, nitroarenofurans, mycotoxins) were even better (r = 0.72-0.95). Addnl., computer automated structure evaluation (CASE) analyses of the nature of the structural determinants associated with each endpoint indicate extensive homologies. The data can be taken to indicate that the two phenomena reflect common mechanisms of action.

Mutagenesis published new progress about Escherichia coli. 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

Kobayashi, Kaoru published the artcileCytotoxic effects of benzbromarone and its 1′-hydroxy metabolite in human hepatocarcinoma FLC4 cells cultured on micro-space cell culture plates, Formula: C13H8Cl2O4S, the main research area is benzbromarone hydroxybenzbromarone CYP3A protein glutathione hepatocellular carcinoma anticancer.

Treatment with benzbromarone (BBR), a potent uricosuric drug, can be associated with liver injury. Recently, we reported that culture of human hepatocellular carcinoma FLC-4 cells on micro-space cell culture plates could increase the functional expression of drug-metabolizing enzymes including CYP3A4 and CYP2C9, which are involved in 1′-hydroxylation and 6-hydroxylation of BBR, resp. Therefore, we examined whether BBR and its two metabolites (1′-hydroxy BBR and 6-hydroxy BBR) have cytotoxic effects in FLC4 cells cultured on micro-space cell culture plates. The present study showed that BBR and 1′-hydroxy BBR, but not 6-hydroxy BBR, have cytotoxic effects in cells cultured on micro-space cell culture plates. BBR-induced cytotoxicity was decreased by CYP3A inhibitors (itraconazole and ketoconazole), an Nrf2 activator (tert-butylhydroquinone) and a GSH precursor (N-acetyl-L-cystein). In contrast, BBR-induced cytotoxicity was increased by a GSH biosynthesis inhibitor (buthionine sulfoximine) and an inhibitor of NAD(P)H quinone oxidoreductase 1 (dicoumarol). These results suggested that metabolic activation of 1′-hydroxy BBR via CYP3A, formation of quinone metabolites and the decrease in GSH levels were involved in the BBR-induced cytotoxicity observed in FLC4 cells cultured on micro-space cell culture plates.

Drug Metabolism and Pharmacokinetics published new progress about Antitumor 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, Formula: C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Aslam, Sana published the artcileAnticancer activity of structural hybrids of various 5/6-memberedheterocycles with pyrazolobenzothiazine 5,5-dioxide, Category: benzothiophene, the main research area is human gastric liver colon carcinoma memberedheterocycle pyrazolobenzothiazine dioxide anticancer.

Thiophene, furan, coumarin and pyrazolobenzothiazine are well familiar for their biol. activities. In this research, pyrazolobenzothiazine ring system is hybridized with various S, N & O-containing heterocycles and the resulting compounds were screened for their anticancer activity against six different cancer cell lines i.e., KB (human oral carcinoma cells), MCF-7(human breast carcinoma cells), A549 (human alveolar adenocarcinoma cells), Hep-G2 (liver carcinoma cells), SGC-7901(human gastric carcinoma cells) and S1 (human colon carcinoma cells) using MTT assay. Most of the compounds exhibited good activity against KB, S1 and A549 cancer cell lines. 5k and 5p appeared as potent inhibitors of KB cell line with IC50 values 2.78 and 4.39 μM resp., 5q was a potent inhibitor of MCF-7 (IC50 value = 13.64 μM) and 5j an excellent inhibitor of A549 cell line having IC50value of 1.03 μM. 5p and 5q were inhibitors of S1 cell line (IC50 values of 8.29 μM and 7.69 μM resp.), whereas, 5o and 5q as inhibitors of Hep-G2 cell line were discovered. A number of compounds show activity exceeding that of 5-fluoruracil in different cell assays. The most potently active compounds, 5j, 5p and 5q, exhibited selectivity in targeting cancerous cells as compared to normal human PBM cells while, 5k and 5o displayed significant toxicity in normal cells.

Pakistan Journal of Pharmaceutical Sciences published new progress about Antitumor agents. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Category: benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Liang, Jinghui published the artcileDesign and development of novel fasudil derivatives as potent antibreast cancer agent that improves intestinal flora and intestinal barrier function in rats, Application In Synthesis of 1468-83-3, the main research area is breast cancer fasudil invasion microbiota migration ROCK; ROCK; breast cancer; fasudil; invasion; microbiota; migration.

This study was conducted to develop novel fasudil derivatives after incorporation of substituted thiazoles as potent anti-breast cancer (BC) agents. The compounds were developed using a facile synthetic route in excellent yields. The entire set of developed compounds was tested for inhibitory activity against rho-associated coiled-coil kinase (ROCK; ROCK1 and ROCK2) kinase, where they exhibit potent and selective inhibition of ROCK1 as compared to ROCK2. The most potent ROCK2 inhibitor, compound 6h significantly inhibited the viability of BC cells (MCF-7). It also causes inhibition of migration and invasion of MCF-7 cells. Moreover, the anti-BC activity of compound 6h was studied in 7,12 di-Me Benz(a)anthracene (DMBA)-induced BC in female Sprague Dawley rats. Results suggest that it causes significant improvement in the bodyweight of the animals with a reduction in oxidative stress in the liver and mammary tissues of rats. It showed improvement in the intestinal barrier function of rats by restoring the level of Diamine oxidase, D-lactate, and endotoxin. In western blot anal., it showed improvement in (ZO-1), occludin, and claudin-1 in the colon tissue of the rat as compared to the DMBA group. Our study demonstrated the development of the novel class of fasudil derivatives potent anti-BC agent that improves intestinal flora and intestinal barrier function in rats.

Chemical Biology & Drug Design published new progress about Antitumor agents. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Application In Synthesis of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Suleiman, Muhammad R. published the artcileDiscovery of small molecule inhibitors through pharmacophore modeling, molecular docking, molecular dynamics simulation and experimental validation against myeloid cell leukemia-1 (Mcl-1), COA of Formula: C13H8Cl2O4S, the main research area is myeloid cell leukemia inhibitor pharmacophore MD simulation; MM/GBSA; Molecular dynamics simulation; Myeloid cell leukemia-1; virtual screening.

Myeloid cell leukemia-1 (Mcl-1) protein is a family of Bcl-2 (B cell lymphoma 2) rich proteases of the most common increase threshold for genetic aberrations observed in human cancer, including lung, breast, pancreatic, cervical, and ovarian cancers as well as leukemia and lymphoma. Mcl-1 is recognized as an attractive drug target in number of diseases, including cancer. In the present study we surveyed and collected queries compounds from PDB database of Mcl-1 protein and generated pharmacophore-based models adapted to screen the drug-like compounds from FDA approved database. The 206 best lead mols. from pharmacophore-screening were further evaluated by mol. docking, mol. dynamics simulation, MM-GBSA calculation, as well as exptl. validation. Two hits, ZINC00601272 and ZINC00002166, showed the best docking scores, which showed a tendency to inhibit cell viability of HL60 and K562 leukemia cells with Mcl-1 expressions. Conclusively, the present study provides structural information of Mcl-1 inhibitors for next generations of cancer therapeutics through computational and exptl. validation approach.

Journal of Biomolecular Structure and Dynamics published new progress about Antitumor 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, COA of Formula: C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Shin, Soon Young published the artcileDesign, synthesis, and biological activities of 1-aryl-(3-(2-styryl)phenyl)prop-2-en-1-ones, Formula: C6H6OS, the main research area is arylstyrylphenylpropenone synthesis antitumor apoptosis ROS; 1-aryl-(3-(2-styryl)phenyl)prop-2-en-1-one; Apoptosis; CoMFA; CoMSIA; Poly(ADP-ribose) polymerase; ROS generation.

A moderate elevation in reactive oxygen species (ROS) levels can generally be controlled in normal cells, but may lead to death of cancer cells as the ROS level in cancer cells is already elevated. Therefore, a ROS-generating compound can act as a selective chemotherapeutic agent for cancer cells that does not affect normal cells. In our previous study, a compound containing a Michael acceptor was selectively cytotoxic to cancer cells without affecting normal cells; therefore, we designed and synthesized 26 compounds containing a Michael acceptor. Their cytotoxicities against HCT116 human colon cancer cell lines were measured by using a clonogenic long-term survival assay. To derive the structural conditions required to obtain stronger cytotoxicity against cancer cells, the relationships between the half-maximal cell growth inhibitory concentration values of the synthesized compounds and their physicochem. properties were evaluated by Comparative Mol. Field Anal. and Comparative Mol. Similarity Indexes Anal. It was confirmed that the compound with the best half-maximal cell growth inhibitory concentration triggered apoptosis through ROS generation, which then led to stimulation of the caspase pathway.

Bioorganic Chemistry published new progress about Antitumor agents. 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

Wu, Pu published the artcileBioactivity-guided discovery of quality control markers in rhizomes of Curcuma wenyujin based on spectrum-effect relationship against human lung cancer cells, Product Details of C6H6OS, the main research area is Curcuma wenyujin rhizome quality control human lung cancer cell; Curcuma wenyujin; bioactive compounds-based fingerprint; quality control; spectrum-effect relationship.

Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs. To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method. The chem. profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle anal. under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical anal. on the chem. composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, resp. Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical anal. uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/mL differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/mL (IC50) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration The spectrum-effect relationship anal. revealed that 44 compounds were pos. correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen pos. correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, β-elemene and β-caryophyllene. Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.

Phytomedicine published new progress about Antitumor agents. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Product Details of C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Belghazi, Maya published the artcileUse of isotopes and LC-MS-ESI-TOF for mechanistic studies of tienilic acid metabolic activation, SDS of cas: 40180-04-9, the main research area is tienilate metabolic activation mechanism cytochrome P 450 2C9.

Tienilic Acid (TA) is a uricosuric drug marketed in 1978 and which caused a number of rare immunoallergic hepatitis. It was withdrawn in the U.S. in 1980, in France in 1992. Early batches of tienilic acid also contained 0.1-0.5 % tienilic acid isomer. Tienilic acid isomer (TAI) has been shown to be metabolized by cytochrome P 450 (CYP) into a reactive thiophene 1-oxide which either binds to proteins, or can be trapped by sulfur nucleophiles. Tienilic acid is metabolized by human CYP 2C9 into 5-hydroxytienilic acid (a major metabolite representing 70 % of the dose excreted in human urine) but it also forms (a) reactive metabolite(s) which binds covalently to CYP 2C9 and it is a mechanism based inhibitor of CYP 2C9. Adding glutathione to incubations decreases the covalent binding, but only to 1 mol/mol P 450. However the reactive metabolite of tienilic acid is still unknown. Recently it has been shown using ESI-LC-MS that CYP 2C9 binds ∼2 mol of TA in absence of GSH and only one in presence of 3 mM GSH. Two pathways of activation of the thiophene ring have been postulated: (A) the arene oxide pathway and (B) the thiophene 1-oxide (or thiophene S-oxide) pathway. In the case of thiophene, benzo(b)thiophene, tienilic acid isomer and several other thiophenes, metabolism through pathway B (thiophene 1-oxide) has been clearly demonstrated. The 1-oxide has only been isolated in the case of benzothiophene. Thus, the aim of the present study was to more carefully examine the metabolic oxidation of tienilic acid using HPLC-MS (LC-ESI-TOF mass spectroscopy) in order to determine which pathway (A or B) is involved in this oxidation For that purpose, labeling experiments with deuterated TA, 1802, 18H2O, and D2O were also performed.

Advances in Experimental Medicine and Biology published new progress about Enzymic oxidation. 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

Fujioka, Yasushi published the artcileRisk assessment of mechanism-based inactivation in drug-drug interactions, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is risk assessment drug interaction CYP inhibitor model; cytochrome P450 inhibitor drug interaction risk assessment model.

Drug-drug interactions (DDIs) that occur via mechanism-based inactivation of cytochrome P 450 are of serious concern. Although several predictive models have been published, early risk assessment of MBIs is still challenging. For reversible inhibitors, the DDI risk categorization using [I]/Ki ([I], the inhibitor concentration; Ki, the inhibition constant) is widely used in drug discovery and development. Although a simple and reliable methodol. such as [I]/Ki categorization for reversible inhibitors would be useful for mechanism-based inhibitors (MBIs), comprehensive anal. of an analogous measure reflecting in vitro potency for inactivation has not been reported. The aim of this study was to evaluate whether the term λ/kdeg (λ, 1st-order inactivation rate at a given MBI concentration; kdeg, enzyme degradation rate constant) would be useful in the prediction of the in vivo DDI risk of MBIs. Twenty-one MBIs with both in vivo area under the curve (AUC) change of marker substrates and in vitro inactivation parameters were identified in the literature and analyzed. The results of this anal. show that in vivo DDIs with >2-fold change of object drug AUC can be identified with the cutoff value of λ/kdeg = 1, where unbound steady-state Cmax is used for inhibitor concentration However, the use of total Cmax led to great overprediction of DDI risk. The risk assessment using λ/kdeg coupled with unbound Cmax can be useful for the DDI risk evaluation of MBIs in drug discovery and development.

Drug Metabolism & Disposition published new progress about Drug interactions. 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

Rao, Sreedhara published the artcileA Refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions, Computed Properties of 40180-04-9, the main research area is QSAR cytochrome P4502C9 drug interaction CoMFA.

A ligand-based model is reported that predicts the Ki values for cytochrome P 450 2C9 (CYP2C9) inhibitors. This CoMFA model was used to predict the affinity of 14 structurally diverse compounds not in the training set and appears to be robust. The mean error of the predictions is 6 μM. The exptl. measured Ki values of the 14 compounds range from 0.1 to 48 μM. Leave-one-out cross-validated partial least-squares gives a q2 value of between 0.6 and 0.8 for the various models which indicates internal consistency. Random assignment of biol. data to structure leads to neg. q2 values. These models are useful in that they establish a pharmacophore for binding to CYP2C9 that can be tested with site-directed mutagenesis. These models can also be used to screen for potential drug interactions and to design compounds that will not bind to this enzyme with high affinity.

Journal of Medicinal Chemistry published new progress about Drug interactions. 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, Computed Properties of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem