Tag: M.W=200-350

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

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

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 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

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

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

Ebenezer, Oluwakemi published the artcileDiscovery of potential inhibitors for RNA-dependent RNA polymerase of Norovirus: virtual screening, and molecular dynamics, Synthetic Route of 55981-09-4, the main research area is CMX521 antiviral agent norwalk virus; CMX521; human norovirus; molecular dynamics; molecular similarity; virtual screening.

Noroviruses are non-enveloped viruses with a pos.-sense single-stranded RNA (ssRNA) genome belonging to the genus Norovirus, from the family Caliciviridae, which are accountable for acute gastroenteritis in humans. The Norovirus genus is subdivided into seven genogroups, i.e., (GI-GVII); among these, the genogroup II and genotype 4 (GII.4) strains caused global outbreaks of human norovirus (HuNov) disease. The viral genome comprises three open reading frames (ORFs). ORF1 encodes the nonstructural polyprotein that is cleaved into six nonstructural proteins, which include 3C-like cysteine protease (3CLpro) and a viral RNA-dependent RNA polymerase. ORF2 and ORF3 encode the proteins VP1 and VP2. The RNA-dependent RNA polymerase (RdRp) from noroviruses is one of the multipurpose enzymes of RNA viruses vital for replicating and transcribing the viral genome, making the virally encoded enzyme one of the critical targets for the development of novel anti-norovirus agents. In the quest for a new antiviral agent that could combat HuNov, high throughput virtual screening (HTVS), combined with e-pharmacophore screening, was applied to screen compounds from the PubChem database. CMX521 mol. was selected as a prototype for a similarity search in the PubChem online database. Mol. dynamics simulations were employed to identify different compounds that may inhibit HuNov. The results predicted that compound CID-57930781 and CID-44396095 formed stable complexes with MNV-RdRp within 50 ns; hence, they may signify as promising human norovirus inhibitors.

International Journal of Molecular Sciences 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, Synthetic Route of 55981-09-4.

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

Riccio, Anna published the artcileImpairment of SARS-CoV-2 spike glycoprotein maturation and fusion activity by nitazoxanide: an effect independent of spike variants emergence, Name: 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, the main research area is SARS COV2 spike glycoprotein nitazoxanide COVID19; Broad-spectrum antiviral; COVID-19; Nitazoxanide; SARS-CoV-2 spike; SARS-CoV-2 variants; Syncytia formation.

SARS-CoV-2, the causative agent of COVID-19, has caused an unprecedented global health crisis. The SARS-CoV-2 spike, a surface-anchored trimeric class-I fusion glycoprotein essential for viral entry, represents a key target for developing vaccines and therapeutics capable of blocking virus invasion. The emergence of SARS-CoV-2 spike variants that facilitate virus spread and may affect vaccine efficacy highlights the need to identify novel antiviral strategies for COVID-19 therapy. Here, we demonstrate that nitazoxanide, an antiprotozoal agent with recognized broad-spectrum antiviral activity, interferes with SARS-CoV-2 spike maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Engineering multiple SARS-CoV-2 variant-pseudoviruses and utilizing quant. cell-cell fusion assays, we show that nitazoxanide-induced spike modifications hinder progeny virion infectivity as well as spike-driven pulmonary cell-cell fusion, a critical feature of COVID-19 pathol. Nitazoxanide, being equally effective against the ancestral SARS-CoV-2 Wuhan-spike and different emerging variants, including the Delta variant of concern, may represent a useful tool in the fight against COVID-19 infections.

Cellular and Molecular Life Sciences 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

Danta, Chhanda Charan published the artcileCNS Penetration Ability: A Critical Factor for Drugs in the Treatment of SARS-CoV-2 Brain Infection, Application of 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, the main research area is drug treatment SARS CoV 2; CNS infection; CNS penetration; COVID19; SARS-CoV-2; drug treatment; log P.

Now, it has been evidenced that Covid19 (SARS-CoV-2) infects the brain tissues. Along with this, a challenge has been raised for research professionals to find effective drugs for its treatment since the recent spread of this virus from Wuhan, China. Targeting the treatment of brain infection, it has also been a challenge that the clin. drug should have good CNS penetration ability to cross the blood-brain barrier.

ACS Chemical Neuroscience 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, Application of 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate.

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