Category: chlorides-buliding-blocks

Wang, Wentian; Zhang, Lu; Morlock, Lorraine; Williams, Noelle S.; Shay, Jerry W.; De Brabander, Jef K. published the artcile< Design and Synthesis of TASIN Analogues Specifically Targeting Colorectal Cancer Cell Lines with Mutant Adenomatous Polyposis Coli (APC)>, Application of C7H5ClF2O3S, the main research area is preparation TASIN analog targeting colorectal cancer.

Despite advances in targeted anticancer therapies, there are still no small-mol.-based therapies available that specifically target colorectal cancer (CRC) development and progression, the second leading cause of cancer deaths. We previously disclosed the discovery of truncating adenomatous polyposis coli (APC)-selective inhibitor 1 (TASIN-1), a small mol. that specifically targets colorectal cancer cells lines with truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor gene through inhibition of cholesterol biosynthesis. Here, we report a medicinal chem. evaluation of a collection of TASIN analogs and activity against colon cancer cell lines and an isogenic cell line pair reporting on the status of APC-dependent selectivity. A number of potent and selective analogs were identified, including compounds with good metabolic stability and pharmacokinetic properties. The compounds reported herein represent a first-in-class genotype-selective series that specifically target apc mutations present in the majority of CRC patients and serve as a translational platform toward a targeted therapy for colon cancer.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 351003-34-4 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H5ClF2O3S, Application of C7H5ClF2O3S.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Qu, Zheng-Wang; Zhu, Hui; Grimme, Stefan published the artcile< Mechanistic Insights for Dimethyl Sulfoxide Catalyzed Aromatic Chlorination Reactions>, Name: 1-Chloropyrrolidine-2,5-dione, the main research area is dimethyl sulfoxide catalyst aromatic chlorination reaction mechanism.

Recently, the DMSO O=SMe2 catalyzed aromatic chlorination reaction using N-chlorosuccinimides (NsCl) under mild conditions has proven useful for bioactive compounds potentially containing various functional groups such as amide and hydroxyl. A novel catalytic mechanism is revealed by extensive DFT calculations using the anisole PhOMe as electron-rich model substrate. The Cl+ transfer from NsCl to O=SMe2 slowly reacts via the S-chloro sulfoxonium O=SClMe2+ to the S-chloro ylide O=SClMeCH2, followed by facile Cl+ transfer from NsCl to the ylide CH2 site to initialize efficient electrophilic Cl+ transfer to nucleophilic substrates. According to the new proposal, the polarizable S and electroneg. O sites of O=SMe2 may act as efficient Cl+ and H+ shuttles, resp., in catalytic aromatic chlorination. If O=SMe2 is present in high concentration, it can trap intermediate SMe2OH+ into a stable H+-bound dimer (SMe2O)2H+ to inhibit efficient protic NsCl activation. These mechanistic insights may be generally useful for the rational design of novel dual functional halonium transfer catalysts.

ChemCatChem published new progress about Activation energy. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Name: 1-Chloropyrrolidine-2,5-dione.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Liu, Jinggong; Liu, Weilin; Ge, Hu; Gao, Jinbo; He, Qingqing; Su, Lijuan; Xu, Jun; Gu, Lian-quan; Huang, Zhi-shu; Li, Ding published the artcile< Syntheses and characterization of non-bisphosphonate quinoline derivatives as new FPPS inhibitors>, Computed Properties of 22717-55-1, the main research area is non bisphosphonate quinoline derivative preparation FPPS geranyltransferase inhibitor cancer; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; Allosteric site; BPs; BSA; Bisphosphonate; Cancer; DL-dithiothreitol; DTT; FPPS; Farnesyl pyrophosphate synthase; HAP; MTT; Quinoline derivative; Tris; bisphosphonates; bovine serum albumin; farnesyl pyrophosphate synthase; hydroxyapatite; tris(hydroxymethyl)aminomethane.

Background: Farnesyl pyrophosphate synthase (FPPS) is a key regulatory enzyme in the biosynthesis of cholesterol and in the post-translational modification of signaling proteins. It has been reported that non-bisphosphonate FPPS inhibitors targeting its allosteric binding pocket are potentially important for the development of promising anti-cancer drugs. Methods: The following methods were used: organic syntheses of non-bisphosphonate quinoline derivatives, enzyme inhibition studies, fluorescence titration assays, synergistic effect studies of quinoline derivatives with zoledronate, ITC studies for the binding of FPPS with quinoline derivatives, NMR-based HAP binding assays, mol. modeling studies, fluorescence imaging assay and MTT assays. Results: We report our syntheses of a series of quinoline derivatives as new FPPS inhibitors possibly targeting the allosteric site of the enzyme. Compound 6b showed potent inhibition to FPPS without significant hydroxyapatite binding affinity. The compound showed synergistic inhibitory effect with active-site inhibitor zoledronate. ITC experiment confirmed the good binding effect of compound 6b to FPPS, and further indicated the binding ratio of 1:1. Mol. modeling studies showed that 6b could possibly bind to the allosteric binding pocket of the enzyme. The fluorescence microscopy indicated that these compounds could get into cancer cells. Conclusions: Our results showed that quinoline derivative 6b could become a new lead compound for further optimization for cancer treatment. General significance: The traditional FPPS active-site inhibitors bisphosphonates show poor membrane permeability to tumor cells, due to their strong polarity. The development of new non-bisphosphonate FPPS inhibitors with good cell membrane permeability is potentially important.

Biochimica et Biophysica Acta, General Subjects published new progress about Antitumor agents. 22717-55-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Computed Properties of 22717-55-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Shim, Soon-Mi; Bae, Eunkyung; Kim, Gun-Hee published the artcile< Single-dose oral acute toxicity and mutagenic effects of methanol extracts of Cirsium japonicum>, Electric Literature of 6055-19-2, the main research area is Cirsium acute oral toxicity mutagenicity chromosome flavone.

The purpose of this study was to evaluate safety on Cirsium japonicum extracts containing flavones by examining acute oral toxicity, bacterial reverse mutation and the chromosome aberration test. Mutagenicity of extracts were evaluated by a bacterial reverse mutation assay using Salmonella typhimurium TA98, TA100, TA102, TA1535, TA1537 and Escherichia coli (WP2uvrA) with and without metabolic activation. An in vitro chromosome aberration test in Chinese hamster lung cells was conducted at the concentrations of 0, 1,250, 2,500 and 5,000 μg/mL. No significant adverse effects on body weight, mortality and gross findings were observed for 15 days after a single dose (2,000 mg of extracts/kg body weight) of administration. In the bacterial reverse mutation assay, C. japonicum extracts ranging from 156 to 5,000 μg/plate did not induce base-pair substitution or frame shift. Any significant increase in structural aberration as well as reduction of cell cycle progression was not observed in the chromosome.

Journal of Food Biochemistry published new progress about Chromosome aberrations. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Electric Literature of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Li, Peng; Furuta, Takeshi; Kobayashi, Takuya published the artcile< Micro-particles as interfering substances in colorimetric residual chlorine measurement>, HPLC of Formula: 128-09-6, the main research area is microparticle interfering substance colorimetric residual chlorine measurement; Chlorination; Colorimetry; Interference; Micro-particle; Residual chlorine; Water treatment.

Conventional methods using o-tolidine and N,N-diethyl-p-phenylenediamine as colorimetric reagents have been extensively applied worldwide in residual chlorine measurement for water quality and environmental management. Different types of interferences resulting in erroneous measurements while using colorimetry have been previously reported. In this study, we exptl. demonstrated micro-particles as interfering substances in selected inorganic (five metal oxidants) and organic (microalgae) particles. The results indicated erroneous measurements (viz. color development) for three of the selected particles. These erroneous measurement levels were evaluated with reference to the chlorine concentration (in mg-Cl2/L, hereafter represented as mg/L) in relation to both representative colorimetric reagents in terms of the amount of particles and time variations. A novel viewpoint that filtration could be a possible solution to the erroneous measurement caused by such micro-particles was proposed.

Ecotoxicology and Environmental Safety published new progress about Color. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, HPLC of Formula: 128-09-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Bhansali, Pravin; Hanigan, Christin L.; Casero, Robert A.; Tillekeratne, L. M. Viranga published the artcile< Largazole and analogues with modified metal-binding motifs targeting histone deacetylases: Synthesis and biological evaluation>, Computed Properties of 19995-38-1, the main research area is peptidomimetic largazole enantioselective synthesis antitumor structure activity chelator zinc; cyclopeptide histone deacetylase inhibitor tubulin acetylation colon carcinoma; cyclocondensation enzymic resolution Wittig reaction aldol condensation; conjugate addition acyl transfer coupling Yamaguchi esterification macrolactamization trityl; chiral auxiliary acetyl Nagao transition state structure.

The histone deacetylase inhibitor largazole was synthesized by a convergent approach that involved several efficient and high yielding single pot multistep protocols. Initial attempts using tert-Bu as thiol protecting group proved problematic, and synthesis was accomplished by switching to the trityl protecting group. This synthetic protocol provides a convenient approach to many new largazole analogs. Three side chain analogs with multiple heteroatoms for chelation with Zn2+ were synthesized, and their biol. activities were evaluated. They were less potent than largazole in growth inhibition of HCT116 colon carcinoma cell line and in inducing increases in global H3 acetylation. Largazole and the three side chain analogs had no effect on HDAC6, as indicated by the lack of increased acetylation of α-tubulin.

Journal of Medicinal Chemistry published new progress about Acetylation. 19995-38-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H7ClS, Computed Properties of 19995-38-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Corton, J. Christopher; Witt, Kristine L.; Yauk, Carole L. published the artcile< Identification of p53 Activators in a Human Microarray Compendium>, Reference of 6055-19-2, the main research area is p53 activation human microarray DNA damage.

Biomarkers predictive of mol. and toxicol. effects are needed to interpret emerging high-throughput transcriptomic data streams. The previously characterized 63 gene TGx-DDI biomarker that includes 20 genes known to be regulated by p53 was previously shown to accurately predict DNA damage in chem.-treated cells. The authors comprehensively evaluated whether the mol. basis of the DDI predictions was based on a p53-dependent response. The biomarker was compared to microarray data in a compendium derived from human cells using the Running Fisher test, a nonparametric correlation test. Using the biomarker, the authors identified conditions that led to p53 activation, including exposure to the chem. nutlin-3 which disrupts interactions between p53 and the neg. regulator MDM2 or by knockdown of MDM2. The expression of most of the genes in the biomarker (75%) were found to depend on p53 activation status based on gene behavior after TP53 overexpression or knockdown. The biomarker identified DDI chems. that were strong inducers of p53 in wild-type cells; these p53 responses were decreased or abolished in cells after p53 knockdown by siRNAs. Using the biomarker, the authors screened ∼1950 chems. in ∼9800 human cell line chem. vs. control comparisons and identified ∼100 chems. that caused p53 activation. Among the pos. chems. were many that are known to activate p53 through direct and indirect DNA damaging mechanisms. These results contribute to the evidence that the TGx-DDI biomarker is useful for identifying chems. that cause DDI and activate p53.

Chemical Research in Toxicology published new progress about Algorithm. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Reference of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Kim, Sou Hyun; Kim, Minwoo; Kwon, Doyoung; Pyo, Jae Sung; Kim, Joo Hyun; Kwak, Jae-Hwan; Jung, Young-Suk published the artcile< N-phenyl cinnamamide derivatives protect hepatocytes against oxidative stress by inducing cellular glutathione synthesis via nuclear factor (erythroid-derived 2)-like 2 activation>, HPLC of Formula: 17082-09-6, the main research area is phenyl cinnamamide preparation antioxidant hepatocyte Nrf2 ARE agonistic activity; N-phenyl cinnamamide; antioxidant response element; glutathione; nuclear factor (erythroid-derived 2)-like 2.

Substituted N-Ph cinnamamide derivatives I (R = OMe, OEt, CN, Cl, N(Me)2) were designed and synthesized to confirm activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway by the electronic effect on beta-position of Michael acceptor according to introducing the R1 and R2 group. Compounds were screened using the Nrf2/antioxidant response element (ARE)-driven luciferase reporter assay. Compound II (R = N(Me)2) showed desirable luciferase activity in HepG2 cells without cell toxicity. MRNA and protein expression of Nrf2/ARE target genes such as NAD(P)H quinone oxidoreductase 1, hemeoxygenase-1, and glutamate-cysteine ligase catalytic subunit (GCLC) were upregulated by compound II (R = N(Me)2) in a concentration-dependent manner. Treatment with compound II (R = N(Me)2) resulted in increased endogenous antioxidant glutathione, showing strong correlation with enhanced GCLC expression for synthesis of glutathione. In addition, tert-Bu hydroperoxide (t-BHP)-generated reactive oxygen species were significantly removed by compound II (R = N(Me)2) , and the results of a cell survival assay in a t-BHP-induced oxidative cell injury model showed a cytoprotective effect of compound II (R = N(Me)2) in a concentration dependent manner. In conclusion, the novel compound II (R = N(Me)2) can be utilized as an Nrf2/ARE activator in antioxidative therapy.

Molecules published new progress about Antioxidants. 17082-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C9H7ClO, HPLC of Formula: 17082-09-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Wang, Siyu; Sun, Minghui; Zhang, Huan; Zhang, Juan; He, Yun; Feng, Zhang published the artcile< Iron-catalyzed borylation and silylation of unactivated tertiary, secondary, and primary alkyl chlorides>, SDS of cas: 19995-38-1, the main research area is tertiary secondary primary alkyl chloride iron catalysis borylation silylation.

Herein, we describe an iron-catalyzed borylation and silylation of unactivated alkyl chlorides, delivering the tertiary, secondary, and primary alkylboronic esters, and secondary, primary alkylsilanes with high efficiency. This protocol exhibits broad substrate scope and good functional group compatibility, allowing the efficient late-stage borylation of biorelevant compounds, thus offering an excellent platform in drug discovery and development. Preliminary mechanistic studies suggest that an alkyl radical was involved in this catalytic system.

CCS Chemistry published new progress about Alkylsilanes Role: PEP (Physical, Engineering or Chemical Process), PROC (Process). 19995-38-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H7ClS, SDS of cas: 19995-38-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Chen, Yuanjin; Ma, Yangyang; Li, Liangkui; Jiang, Hao; Li, Zhiping published the artcile< Nitration-Peroxidation of Alkenes: A Selective Approach to β-Peroxyl Nitroalkanes>, Computed Properties of 1592-20-7, the main research area is peroxyl nitroalkane preparation nitration peroxidation alkene Bu nitrite hydroperoxide.

Nitration-peroxidation of alkenes for the synthesis of β-peroxyl nitroalkanes has been developed by using tert-Bu nitrite and tert-Bu hydroperoxide. The method presents a new and selective difunctionalization of alkenes to introduce a nitro group and a peroxyl group across the double bonds of alkenes under mild conditions. A radical reaction pathway is proposed by exptl. and theor. studies. Of note, mixing a metal salt and peroxide can cause an explosion.

Organic Letters published new progress about Alkanes, nitro Role: SPN (Synthetic Preparation), PREP (Preparation) (β-peroxyl). 1592-20-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C9H9Cl, Computed Properties of 1592-20-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics