Category: esters-buliding-blocks

Bordicchia, Matteo published the artcileFeline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and In Vitro Efficacy of Novel Antivirals in Australian Outbreaks, Name: 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, the main research area is sequence antiviral agent feline calicivirus upper respiratory tract disease; 2�C-methylcytidine; Caliciviridae; NITD-008; Vesivirus; nitazoxanide.

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiol. and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2′-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Anal. of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6μM, TI = 21; 2CMC EC50, 2.7-5.3μM, TI > 18; NITD-008, 0.5 to 0.9μM, TI > 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted. Feline calicivirus sequence has been deposited in GenBank under accession number MW880757-MW880771.

Viruses 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, Name: 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate.

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

Nunes, Damiana Antonia de Fatima published the artcileNS2B-NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review, Formula: C12H9N3O5S, the main research area is protease inhibitor antiviral agents zika virus infection enzymic inhibition; NS2B-NS3 protease; Zika virus; antiviral; enzymatic inhibition; noncompetitive inhibitors.

Zika virus (ZIKV) infections are associated with severe neurol. complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising mol. target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 ΜM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 ΜM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 ΜM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases.

Journal of Medical Virology 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, Formula: C12H9N3O5S.

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

Hattori, Shin-Ichiro published the artcileGRL-0920, an indole chloropyridinyl ester, completely blocks SARS-CoV-2 infection, Formula: C12H9N3O5S, the main research area is SARSCoV2 indole chloropyridinyl ester replication; COVID-19; SARS-CoV-2; antiviral agents; main protease.

We assessed various newly generated compounds that target the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and various previously known compounds reportedly active against SARS-CoV-2, employing RNA quant. PCR (RNA-qPCR), cytopathicity assays, and immunocytochem. Here, we show that two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, exerted potent activity against SARS-CoV-2 in cell-based assays performed using VeroE6 cells and TMPRSS2-overexpressing VeroE6 cells. While GRL-0820 and the nucleotide analog remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred. No significant anti-SARS-CoV-2 activity was found for several compounds reportedly active against SARS-CoV-2 such as lopinavir, nelfinavir, nitazoxanide, favipiravir, and hydroxychroloquine. In contrast, GRL-0920 exerted potent activity against SARS-CoV-2 (50% effective concentration [EC50] = 2.8μM) and dramatically reduced the infectivity, replication, and cytopathic effect of SARS-CoV-2 without significant toxicity as examined with immunocytochem. Structural modeling shows that indole and chloropyridinyl of the derivatives interact with two catalytic dyad residues of Mpro, Cys145 and His41, resulting in covalent bonding, which was verified using high-performance liquid chromatog.-mass spectrometry (HPLC/MS), suggesting that the indole moiety is critical for the anti-SARS-CoV-2 activity of the derivatives GRL-0920 might serve as a potential therapeutic for coronavirus disease 2019 (COVID-19) and might be optimized to generate more-potent anti-SARS-CoV-2 compounds IMPORTANCE Targeting the main protease (Mpro) of SARS-CoV-2, we identified two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, active against SARS-CoV-2, employing RNA-qPCR and immunocytochem. and show that the two compounds exerted potent activity against SARS-CoV-2. While GRL-0820 and remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred as examined with immunocytochem. In contrast, GRL-0920 completely blocked the infectivity and cytopathic effect of SARS-CoV-2 without significant toxicity. Structural modeling showed that indole and chloropyridinyl of the derivatives interacted with two catalytic dyad residues of Mpro, Cys145 and His41, resulting in covalent bonding, which was verified using HPLC/MS. The present data should shed light on the development of therapeutics for COVID-19, and optimization of GRL-0920 based on the present data is essential to develop more-potent anti-SARS-CoV-2 compounds for treating COVID-19.

mBio 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, Formula: C12H9N3O5S.

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

Dou, Dengfeng published the artcilePotent norovirus inhibitors based on the acyclic sulfamide scaffold, Formula: C6H14ClNO2, the main research area is preparation norovirus antiviral acyclic sulfamide scaffold.

The development of small mol. therapeutics to combat norovirus infection is of considerable interest from a public health perspective because of the highly contagious nature of noroviruses. A series of amino acid-derived acyclic sulfamide-based norovirus inhibitors has been synthesized and evaluated using a cell-based replicon system. Several compounds were found to display potent anti-norovirus activity, low toxicity, and good aqueous solubility These compounds are suitable for further optimization of pharmacol. and ADMET properties.

Bioorganic & Medicinal Chemistry published new progress about Antiviral agents. 10047-10-6 belongs to class esters-buliding-blocks, name is Methyl 2-aminopentanoate hydrochloride, and the molecular formula is C6H14ClNO2, Formula: C6H14ClNO2.

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

Chen, Yuefang published the artcileSynergy of Al2(SO4)3 and H3PO4 in co-solvents converts starch to 5-ethoxymethylfurfural, Computed Properties of 539-88-8, the main research area is synergy Al2SO4 H3PO4 solvent starch ethoxymethylfurfural.

Efficient synthesis of promising biofuel 5-ethoxymethylfurfural (EMF) directly from starch was developed over a mixed-acid system composed of Al2(SO4)3 and H3PO4 in ethanol-DMSO co-solvent medium. The reaction proceeds through the depolymerization of starch to form glucose over Bronsted acidic H3PO4, which is then isomerized to fructose by Al2(SO4)3, a Lewis acid catalyst. The mixed-acid system then synergistically catalyzes the formation of EMF. At 170°C, 36.9%, 39.8%, and 34.7% yields of EMF can be captured from corn starch, amylose and amylopectin, resp. Moreover, the conversion of cellobiose and wood pulp cellulose produces 38.5% and 9.5% yields of EMF.

Catalysis Communications published new progress about Aprotic solvents. 539-88-8 belongs to class esters-buliding-blocks, name is Ethyl 4-oxopentanoate, and the molecular formula is C7H12O3, Computed Properties of 539-88-8.

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

Li, Jian-Feng published the artcileStructural characterization and aquatic toxicity prediction of esters, Safety of Methyl decanoate, the main research area is aquatic toxicity ester compound structure relationship.

Based on the three-dimensional structures of the compounds, the structures of 48 ester compounds were expressed parametrically. Through multiple linear regression and partial least-squares regression, the relationship models between ester compound structures and aquatic toxicity log(1/IGC50) were established. The correlation coefficients (R2) of the models were 0.9974 and 0.9940, and the standard deviations (SD) were 0.0469 and 0.0646, resp. The stability of the models was evaluated by the leave-one-out internal cross-test. The correlation coefficients (RCV2) of the models of interactive tests were 0.9939 and 0.8952, and the standard deviation (SDCV) was 0.0715 and 0.0925, resp. The external samples were used to test the predictive ability of the models, and the correlation coefficients (Rtest2) of the external predictions were 0.9955 and 0.9955, and the standard deviations (SDtest) were 0.0720 and 0.0716, resp. The mol. structure descriptors could successfully represent the structural characteristics of the compounds, and the built models had good fitting effects, strong stability and high prediction accuracy. The present study has a good reference value for the study of the structure-toxicity relationship of toxic compounds in the environment.

Chinese Journal of Structural Chemistry published new progress about Aquatic toxicity. 110-42-9 belongs to class esters-buliding-blocks, name is Methyl decanoate, and the molecular formula is C11H22O2, Safety of Methyl decanoate.

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

Kim, Ho Shin published the artcileImprovement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M, HPLC of Formula: 623-50-7, the main research area is carcinoma DCN1 UBE2M interaction inhibitors NEDD8 pharmacokinetic oral bioavailability.

The cullin-RING ubiquitin ligases (CRLs) are ubiquitin E3 enzymes that play a key role in controlling proteasomal degradation and are activated by neddylation. We previously reported inhibitors that target CRL activation by disrupting the interaction of defective in cullin neddylation 1 (DCN1), a CRL neddylation co-E3, and UBE2M, a neddylation E2. Our first-generation inhibitors possessed poor oral bioavailability and fairly rapid clearance that hindered the study of acute inhibition of DCN-controlled CRL activity in vivo. Herein, we report studies to improve the pharmacokinetic performance of the pyrazolo-pyridone inhibitors. The current best inhibitor, 40 (I), inhibits the interaction of DCN1 and UBE2M, blocks NEDD8 transfer in biochem. assays, thermally stabilizes cellular DCN1, and inhibits anchorage-independent growth in a DCN1 amplified squamous cell carcinoma cell line. Addnl., we demonstrate that a single oral 50 mg/kg dose sustains plasma exposures above the biochem. IC90 for 24 h in mice.

Journal of Medicinal Chemistry 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, HPLC of Formula: 623-50-7.

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

Xu, Qingbo published the artcileManganese porphyrin-based metal-organic framework for synergistic sonodynamic therapy and ferroptosis inhypoxic tumors, Category: esters-buliding-blocks, the main research area is manganese porphyrin metal organic framework sonodynamic therapy ferroptosis; GSH depletion; catalase-like activity; ferroptosis; metal-organic framework; reactive oxygen species; sonodynamic therapy.

Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy. However, the SDT efficacy is severely limited by the hypoxia and high glutathione (GSH) in the tumor microenvironment, and ferroptosis is highly associated with reactive oxygen species (ROS) and GSH depletion. A manganese porphyrin-based metal-organic framework (Mn-MOF) was constructed as a nanosensitizer to self-supply oxygen (O2) and decrease GSH for enhanced SDT and ferroptosis. In vitro and in vivo anal., including characterization, O2 generation, GSH depletion, ROS generation, lipid peroxidation, antitumor efficacy and tumor immune microenvironment were systematically evaluated. Mn-MOF exhibited catalase-like and GSH decreasing activity in vitro. After efficient internalization into cancer cells, Mn-MOF persistently catalyzed tumor-overexpressed H2O2 to in-situ produce O2 to relieve tumor hypoxia and decrease GSH and GPX4, which facilitated the formation of ROS and ferroptosis to kill cancer cells upon US irradiation in hypoxic tumors. Thus, strong anticancer and anti-metastatic activity was found in H22 and 4T1 tumor-bearing mice after a single administration of Mn-MOF upon a single US irradiation In addition, Mn-MOF showed strong antitumor immunity and improved immunosuppressive microenvironment upon US irradiation by increasing the numbers of activated CD8+ T cells and matured dendritic cells and decreaing the numbers of myeloid-derived suppressor cells in tumor tissues. Mn-MOF holds great potential for hypoxic cancer therapy.

Theranostics 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, Category: esters-buliding-blocks.

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

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