Month: December 2022

Borin, Alexandre published the artcileIdentification and characterization of the anti-SARS-CoV-2 activity of cationic amphiphilic steroidal compounds, Product Details of C12H9N3O5S, the main research area is remdesivir antiviral agent SARS CoV 2 steroidal compound; SARS-CoV-2; antiviral activity; drug discovery; steroidal compounds.

The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening campaigns using a cytopathic effect-based assay in Vero CCL81 cells, followed by hit compound validation and characterization. Compounds LNB167 and LNB169 were selected due to their ability to reduce the levels of infectious viral progeny and viral RNA levels in Vero CCL81, HEK293, and HuH7.5 cell lines. Mechanistic studies in Vero CCL81 cells indicated that LNB167 and LNB169 inhibited the initial phase of viral replication through mechanisms involving modulation of membrane lipids and cholesterol in host cells. Selection of viral variants resistant to steroidal compound treatment revealed single mutations on transmembrane, lipid membrane-interacting Spike and Envelope proteins. Finally, in vivo testing using the hACE2 transgenic mouse model indicated that SARS-CoV-2 infection could not be ameliorated by LNB167 treatment. We conclude that anti-SARS-CoV-2 activities of steroidal compounds LNB167 and LNB169 are likely host-targeted, consistent with the properties of cationic amphiphilic compounds that modulate host cell lipid biol. Although effective in vitro, protective effects were cell-type specific and did not translate to protection in vivo, indicating that subversion of lipid membrane physiol. is an important, yet complex mechanism involved in SARS-CoV-2 replication and pathogenesis.

Virulence published new progress about Antiviral agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Product Details of C12H9N3O5S.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Cui, Zhanding published the artcileNitazoxanide protects cats from feline calicivirus infection and acts synergistically with mizoribine in vitro, Recommanded Product: 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, the main research area is nitazoxanide mizoribine antiviral agent feline calicivirus infection; Antiviral; Feline calicivirus; In vivo; Mizoribine; Nitazoxanide.

Feline calicivirus (FCV) is a highly contagious pathogen that causes acute upper respiratory infections and oral disease in cats, thus seriously endangering feline health. Recently, there have been outbreaks of particularly virulent variant strains of FCV, which can cause both acute symptoms and fatal systemic disease. The discovery of effective antiviral agents to treat FCV infection is, therefore, gradually assuming increased importance. In this study, we showed that both nitazoxanide and mizoribine had antiviral activity in F81 cells infected with different strains of FCV and also demonstrated a synergistic effect between the two drugs. Experiments in cats challenged with FCV showed that nitazoxanide significantly reduced the clin. symptoms of FCV infection, reduced viral load in the trachea and lungs, and reduced viral shedding. Our results showed that nitazoxanide and mizoribine could potentially be used as therapeutic agents to treat FCV infection.

Antiviral Research published new progress about Antiviral agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Recommanded Product: 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Omar, Sara Ibrahim published the artcileRanking the Binding Energies of p53 Mutant Activators and Their ADMET Properties, Application In Synthesis of 72835-26-8, the main research area is p53 activator antitumor binding pharmacokinetics; ADMET properties; MD simulations; P53 activators; docking; p53-R273H.

The guardian of the genome, p53, is the most mutated protein found in all cancer cells. Restoration of wild-type activity to mutant p53 offers promise to eradicate cancer cells using novel pharmacol. agents. Several mols. have already been found to activate mutant p53. While the exact mechanism of action of these compounds has not been fully understood, a transiently open pocket has been identified in some mutants. In our study, we docked twelve known activators to p53 into the open pocket to further understand their mechanism of action and rank the best binders. In addition, we predicted the absorption, distribution, metabolism, excretion and toxicity properties of these compounds to assess their pharmaceutical usefulness. Our studies showed that alkylating ligands do not all bind at the same position, probably due to their varying sizes. In addition, we found that non-alkylating ligands are capable of binding at the same pocket and directly interacting with Cys124. The comparison of the different ligands demonstrates that stictic acid has a great potential as a p53 activator in terms of less adverse effects although it has poorer pharmacokinetic properties.

Chemical Biology & Drug Design published new progress about Antitumor agents. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Application In Synthesis of 72835-26-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Mowery, Patricia published the artcileDiscovery of an indole-substituted furanone with tubulin polymerization inhibition activity, Application of Ethyl 2-hydroxyacetate, the main research area is indole furanone drug discovery synthesis anticancer tubulin polymerization inhibition; Anticancer; Furanone; Indole; Tubulin.

Analogs of diarylpyrrolinone lead compound I were prepared and tested for anti-proliferative activity in U-937 cancer cells. Alterations of I focused on modifying the two nitrogen atoms: the pyrrolinone nitrogen atom was substituted with a Pr group or replaced with an oxygen atom (furanone); and the substituents on the indole nitrogen were varied. These changes led to the discovery of a furanone analog II with sub-micromolar anti-cancer potency and tubulin polymerization inhibition activity.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 623-50-7 belongs to class esters-buliding-blocks, name is Ethyl 2-hydroxyacetate, and the molecular formula is C4H8O3, Application of Ethyl 2-hydroxyacetate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Abdel Raoof, Gehan F. published the artcileCytotoxic effect and phytochemical study of petroleum ether extract of Tilia cordata mill, SDS of cas: 110-42-9, the main research area is Tilia petroleum ether extract anticancer cytotoxicity cancer.

Objective: The aim of this research was to investigate the chem. composition of petroleum ether extract of Tilia cordata aerial parts as well as to evaluate its cytotoxic activity. Methods: Gas chromatog. and gas chromatog.-mass spectrometry (GC-MS) were used to analyze the unsaponifiable matter and fatty acid Me esters. Moreover, the cytotoxicity was examined against human hepatoma HepG2 cell line and breast adenocarcinoma MCF cell line. Results: The result showed that thirteen compounds were identified in the fatty acid Me esters fraction representing 93.71% of the total identified peak area. The major compounds were Octadecanoic acid Me ester (36.26%) and eicosanoic acid Me ester (29.42%), whereas nineteen compounds in the unsaponifiable fraction were identified representing 90.56 % of the total beak area. The major compounds were 1-Nonene (30.44%), 1-Hexadecene (24.83%) and phytol (10.40%). Moreover, petroleum ether extract showed a potent cytotoxic effect against human hepatoma HepG2 cell line and a moderate cytotoxic effect on breast adenocarcinoma MCF7 human tumor cell line. Conclusion: So the current research aims to be the first step toward the use of petroleum ether extract of Tilia cordata aerial parts as a potent cytotoxic drug.

Universal Journal of Pharmaceutical Research published new progress about Antitumor agents. 110-42-9 belongs to class esters-buliding-blocks, name is Methyl decanoate, and the molecular formula is C11H22O2, SDS of cas: 110-42-9.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Lu, Zirui published the artcileStructure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors, Quality Control of 55981-09-4, the main research area is thiazolides nitazoxanide antitumor STAT3 pathway inhibitor.

We identified nitazoxanide (NTZ) as a moderate STAT3 pathway inhibitor through immunoblot anal. and a cell-based IL-6/JAK/STAT3 pathway activation assay. A series of thiazolide derivatives were designed and synthesized to further validate the thiazolide scaffold as STAT3 inhibitors. Eight out of 25 derivatives displayed potencies greater than that of NTZ, and their STAT3 pathway inhibitory activities were found to be significantly correlated with their antiproliferative activities in HeLa cells. Derivatives 15 and 24 were observed to be more potent than the pos. control WP1066, which is under phase I clin. trials. Compared with NTZ, 15(I) also exhibited much improved in vivo pharmacokinetic parameters in rats and efficacies against proliferations in multiple cancer cell lines, indicating a broad-spectrum effect of these thiazolides as antitumor agents targeted on STAT3.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Quality Control of 55981-09-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reiniers, Megan J. published the artcileAnalysis and optimization of conditions for the use of 2′,7′-dichlorofluorescein diacetate in cultured hepatocytes, HPLC of Formula: 2044-85-1, the main research area is hepatocyte oxidative stress 2 7 dichlorofluorescein diacetate optimization; anoxia and reoxygenation; cellular uptake and export; fluorogenic redox probe; hepatocytes; intravital fluorescence imaging; liver diseases; oxidative and nitrosative stress.

Numerous liver pathologies encompass oxidative stress as mol. basis of disease. The use of 2′,7′-dichlorodihydrofluorescein-diacetate (DCFH2-DA) as fluorogenic redox probe is problematic in liver cell lines because of membrane transport proteins that interfere with probe kinetics, among other reasons. The properties of DCFH2-DA were analyzed in hepatocytes (HepG2, HepaRG) to characterize methodol. issues that could hamper data interpretation and falsely skew conclusions. Experiments were focused on probe stability in relevant media, cellular probe uptake/retention/excretion, and basal oxidant formation and metabolism DCFH2-DA was used under optimized exptl. conditions to intravitally visualize and quantify oxidative stress in real-time in HepG2 cells subjected to anoxia/reoxygenation. The most important findings were that: (1) the non-fluorescent DCFH2-DA and the fluorescent DCF are rapidly taken up by hepatocytes, (2) DCF is poorly retained in hepatocytes, and (3) DCFH2 oxidation kinetics are cell type-specific. Furthermore, (4) DCF fluorescence intensity was pH-dependent at pH < 7 and (5) the stability of DCFH2-DA in cell culture medium relied on medium composition The use of DCFH2-DA to measure oxidative stress in cultured hepatocytes comes with methodol. and tech. challenges, which were characterized and solved. Optimized in vitro and intravital imaging protocols were formulated to help researchers conduct proper experiments and draw robust conclusions. Antioxidants published new progress about Antitumor agents. 2044-85-1 belongs to class esters-buliding-blocks, name is 2',7'-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-3',6'-diyl diacetate, and the molecular formula is C24H14Cl2O7, HPLC of Formula: 2044-85-1.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Steinmetz, Julia published the artcileDescriptive Proteome Analysis to Investigate Context-Dependent Treatment Responses to OXPHOS Inhibition in Colon Carcinoma Cells Grown as Monolayer and Multicellular Tumor Spheroids, Application of 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, the main research area is proteome analysis context dependent OXPHOS inhibition tumor spheroids.

We have previously identified selective upregulation of the mevalonate pathway genes upon inhibition of oxidative phosphorylation (OXPHOS) in quiescent cancer cells. Using mass spectrometry-based proteomics, we here investigated whether these responses are corroborated on the protein level and whether proteomics could yield unique insights into context-dependent biol. HCT116 colon carcinoma cells were cultured as monolayer cultures, proliferative multicellular tumor spheroids (P-MCTS), or quiescent (Q-MCTS) multicellular tumor spheroids and exposed to OXPHOS inhibitors: nitazoxanide, FCCP, oligomycin, and salinomycin or the HMG-CoA-reductase inhibitor simvastatin at two different doses for 6 and 24 h. Samples were processed using an in-depth bottom-up proteomics workflow resulting in a total of 9286 identified protein groups. Gene set enrichment anal. showed profound differences between the three cell systems and confirmed differential enrichment of hypoxia, OXPHOS, and cell cycle progression-related protein responses in P-MCTS and Q-MCTS. Treatment experiments showed that the observed drug-induced alterations in gene expression of metabolically challenged cells are not translated directly to the protein level, but the results reaffirmed OXPHOS as a selective vulnerability of quiescent cancer cells. This work provides rationale for the use of deep proteome profiling to identify context-dependent treatment responses and encourages further studies investigating metabolic processes that could be co-targeted together with OXPHOS to eradicate quiescent cancer cells.

ACS Omega published new progress about Antitumor agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Application of 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Lu, Zirui published the artcileNitazoxanide and related thiazolides induce cell death in cancer cells by targeting the 20S proteasome with novel binding modes, SDS of cas: 55981-09-4, the main research area is nitazoxanide thiazolide preparation proteasome inhibitor antitumor activity; 20S proteasome; Anti-tumor; Nitazoxanide; Thiazolides.

Nitazoxanide and related thiazolides are a novel class of anti-infectious agents against protozoan parasites, bacteria and viruses. In recent years, it is demonstrated that thiazolides can also induce cell cycle arrest and apoptotic cell death in cancer cells. Due to their fast proliferating nature, cancer cells highly depend on the proteasome system to remove aberrant proteins. Many of these aberrant proteins are regulators of cell cycle progression and apoptosis, such as the cyclins, BCL2 family members and nuclear factor of κB (NF-κB). Here, we demonstrate at both mol. and cellular levels that the 20S proteasome is a direct target of NTZ and related thiazolides. By concurrently inhibiting the multiple catalytic subunits of 20S proteasome, NTZ promotes cell cycle arrest and triggers cell death in colon cancer cells, either directly or as a sensitizer to other anti-tumor agents, especially doxorubicin. We further show that the binding mode of NTZ in the β5 subunit of the 20S proteasome is different from that of bortezomib and other existing proteasome inhibitors. These findings provide new insights in the design of novel small mol. proteasome inhibitors as anti-tumor agents suitable for solid tumor treatment in an oral dosing form.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about Antitumor agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, SDS of cas: 55981-09-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Ripani, P. published the artcileThiazolides promote G1 cell cycle arrest in colorectal cancer cells by targeting the mitochondrial respiratory chain, Formula: C12H9N3O5S, the main research area is colorectalcancer cell cycle arrest nitazoxanide RM4819 anticancer proliferation.

Systemic toxicity and tumor cell resistance still limit the efficacy of chemotherapy in colorectal cancer. Therefore, alternative treatments are desperately needed. The thiazolide Nitazoxanide (NTZ) is an FDA-approved drug for the treatment of parasite-mediated infectious diarrhea with a favorable safety profile. Interestingly, NTZ and the thiazolide RM4819-its bromo-derivative lacking antibiotic activity-are also promising candidates for cancer treatment. Yet the exact anticancer mechanism(s) of these compounds still remains unclear. In this study, we systematically investigated RM4819 and NTZ in 2D and 3D colorectal cancer culture systems. Both compounds strongly inhibited proliferation of colon carcinoma cell lines by promoting G1 phase cell cycle arrest. Thiazolide-induced cell cycle arrest was independent of the p53/p21 axis, but was mediated by inhibition of protein translation via the mTOR/c-Myc/p27 pathway, likely caused by inhibition of mitochondrial respiration. While both thiazolides demonstrated mitochondrial uncoupling activity, only RM4819 inhibited the mitochondrial respiratory chain complex III. Interestingly, thiazolides also potently inhibited the growth of murine colonic tumoroids in a comparable manner with cisplatin, while in contrast to cisplatin thiazolides did not affect the growth of primary intestinal organoids. Thus, thiazolides appear to have a tumor-selective antiproliferative activity, which offers new perspectives in the treatment of colorectal cancer.

Oncogene published new progress about Antitumor agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Formula: C12H9N3O5S.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics