Month: October 2022

Bischof, Joachim; Leban, Johann; Zaja, Mirko; Grothey, Arnhild; Radunsky, Barbara; Othersen, Olaf; Strobl, Stefan; Vitt, Daniel; Knippschild, Uwe published the artcile< 2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε>, Electric Literature of 162046-61-9, the main research area is benzamidobenzoimidazolylthiazolecarboxamide derivative preparation inhibition casein kinase 1 isoenzyme antitumor; crystal structure casein kinase isoenzyme inhibitor complex.

In this study two heterocyclic compounds (5 and 6) were identified as potent and specific inhibitors of CK1δ (IC50 = 0.040 and 0.042 μM, resp.). Whereas compound 5 exhibited 5-fold higher affinity toward CK1δ than to CK1ε (IC50 CK1ε = 0.199 μM), compound 6 also inhibited CK1ε (IC50 = 0.0326 μM) in the same range as CK1δ. Selected compound 5 was screened over 442 kinases identifying 5 as a highly potent and selective inhibitor of CK1δ. X-ray anal. of 5 bound to CK1δ demonstrated its binding mode. In addition, characterization of 5 and 6 in a cell biol. approach revealed the ability of both compounds to inhibit proliferation of tumor cell lines in a dose and cell line specific manner. In summary, these optimizations lead to the development of new highly selective CK1δ and ε specific inhibitors with biol. activity.

Amino Acids published new progress about Antitumor agents. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Electric Literature of 162046-61-9.

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

Al-Katib, Ayad; Arnold, Alan A.; Aboukameel, Amro; Sosin, Angela; Smith, Peter; Mohamed, Anwar N.; Beck, Frances W.; Mohammad, Ramzi M. published the artcile< I-kappa-kinase-2 (IKK-2) inhibition potentiates vincristine cytotoxicity in non-Hodgkin's lymphoma>, Category: chlorides-buliding-blocks, the main research area is ML120B vincristine nonHodgkin lymphoma IKK2 NFkappaB anticancer.

Background: IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin’s lymphoma. Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small mol. inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), doxorubicin (H) or vincristine (V) was evaluated in vitro using short-term culture assay. We also determined efficacy of the combination in vivo using the SCID mouse xenografts. Results: ML120B down-regulated p-IκBα protein expression in a concentration dependent manner, caused growth inhibition, increased G0/G1 cells, but did not induce apoptosis. There was no significant enhancement of cell kill in the M/C or M/H combination. However, there was strong synergy in the M/V combination where the vincristine concentration can be lowered by a hundred fold in the combination for comparable G2/M arrest and apoptosis. ML120B prevented vincristine-induced nuclear translocation of p65 subunit of NF-κB. In vivo, ML120B was effective by itself and enhanced CHOP anti-tumor activity significantly (P = 0.001) in the WSU-DLCL2-SCID model but did not prevent CNS lymphoma in the WSU-FSCCL-SCID model. Conclusions: For the first time, this study demonstrates that perturbation of IKK-2 by ML120B leads to synergistic enhancement of vincristine cytotoxicity in lymphoma. These results suggest that disruption of the NF-κB pathway is a useful adjunct to cytotoxic chemotherapy in lymphoma.

Molecular Cancer published new progress about Antitumor agents. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Category: chlorides-buliding-blocks.

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

Rotroff, Daniel M.; Martin, Matt T.; Dix, David J.; Filer, Dayne L.; Houck, Keith A.; Knudsen, Thomas B.; Sipes, Nisha S.; Reif, David M.; Xia, Menghang; Huang, Ruili; Judson, Richard S. published the artcile< Predictive Endocrine Testing in the 21st Century Using in Vitro Assays of Estrogen Receptor Signaling Responses>, Product Details of C7H17Cl2N2O3P, the main research area is estrogen receptor signaling endocrine disrupter high throughput screening.

Thousands of environmental chems. are subject to regulatory review for their potential to be endocrine disruptors (ED). In vitro high-throughput screening (HTS) assays have emerged as a potential tool for prioritizing chems. for ED-related whole-animal tests. In this study, 1814 chems. including pesticide active and inert ingredients, industrial chems., food additives, and pharmaceuticals were evaluated in a panel of 13 in vitro HTS assays. The panel of in vitro assays interrogated multiple end points related to estrogen receptor (ER) signaling, namely binding, agonist, antagonist, and cell growth responses. The results from the in vitro assays were used to create an ER Interaction Score. For 36 reference chems., an ER Interaction Score >0 showed 100% sensitivity and 87.5% specificity for classifying potential ER activity. The magnitude of the ER Interaction Score was significantly related to the potency classification of the reference chems. ERα/ERβ selectivity was also evaluated, but relatively few chems. showed significant selectivity for a specific isoform. When applied to a broader set of chems. with in vivo uterotrophic data, the ER Interaction Scores showed 91% sensitivity and 65% specificity. Overall, this study provides a novel method for combining in vitro concentration response data from multiple assays and, when applied to a large set of ER data, accurately predicted estrogenic responses and demonstrated its utility for chem. prioritization.

Environmental Science & Technology published new progress about Anise oil Role: ADV (Adverse Effect, Including Toxicity), BIOL (Biological Study). 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Product Details of C7H17Cl2N2O3P.

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

Roberts, Dean D.; McLaughlin, Mark G. published the artcile< Regioselective Synthesis of Multifunctional Allylic Amines; Access to Ambiphilic Aziridine Scaffolds>, Synthetic Route of 22952-32-5, the main research area is allylic amine ambiphilic aziridine preparation regioselective; propargylic amine dimethylphenylsilane hydrosilylation platinum chloride XantPhos catalyst.

A highly regioselective hydrosilylation of propargylic amines has been described here for the first time. The reaction utilizes a PtCl2/XantPhos catalyst system to deliver hydrosilanes across the alkyne to afford multifunctional allylic amines in high yields. The reaction is tolerant to a wide variety of functional groups and provides high value intermediates with two distinct functional handles. The synthetic applicability of the reaction has been shown through the synthesis of diverse ambiphilic aziridines.

Organic Letters published new progress about Allyl amines Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 22952-32-5 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O3S, Synthetic Route of 22952-32-5.

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

Verma, Krishan K.; Singh, Umesh K.; Jain, Jainendra published the artcile< Screening of Some Novel 4, 5 Disubstituted 1, 2, 4-Triazole-3-thiones for Anticonvulsant Activity>, Name: Methyl 2,3-dichlorobenzoate, the main research area is triazole thione anticonvulsant drug screening; GABA-AT; MES; Triazol-3-thiones; anticonvulsant activity; docking; scPTZ..

In the present study, we synthesized fifteen 4, 5-disubstituted 1, 2, 4-triazol- 3-thione derivatives and evaluated for anticonvulsant activity with neurotoxicity determination The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The mol. docking study was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software. The anticonvulsant activity was assessed by maximal electroshock (MES) test and s.c. pentylenetetrazol (scPTZ) tests. The neurotoxicity was assessed by rotarod ataxia test. In MES test, compounds 5a, 8a and 9a were found active at 100 mg/kg and five compounds were found active at 300 mg/kg dose after 1 h of administration. After 4 h of drug administration, only two compounds 8a and 9a exhibited protection at 100 mg/kg. In scPTZ test, three compounds 2a, 6a and 8a were found active at 100 mg/kg and 7a was active at 300 mg/kg after 1 h of test drug administration. Most of the compounds were found active in MES test with 8a and 9a being the most active among all. In docking study, 2a was found to be best compound based on the binding energy of -6.5 kcal/mol and estimated inhibition constant of 17.2μM. Majority of synthesized compounds were found active in MES test, whereas only few were found to possess anti scPTZ activity. Among all compounds, only 14a caused motor coordination impairment in rotarod ataxia test at 300 mg/kg 1 h duration.

Central Nervous System Agents in Medicinal Chemistry published new progress about Anticonvulsants. 2905-54-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6Cl2O2, Name: Methyl 2,3-dichlorobenzoate.

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

Alhazmi, Razan; Tong, Shirley; Darwish, Shaban; Khanjani, Elina; Khungar, Bharti; Chawla, Swati; Zheng, Zhonghui; Chamberlin, Richard; Parang, Keykavous; Yang, Sun published the artcile< Bis-Cinnamamide Derivatives as APE/Ref-1 Inhibitors for the Treatment of Human Melanoma>, Quality Control of 17082-09-6, the main research area is cinnamamide derivative APE inhibitor treatment human melanoma; APE/Ref-1; human melanoma; reactive oxygen species (ROS); redox regulation; small molecular inhibitors.

Human malignant melanoma exhibits imbalances in redox status, leading to activation of many redox-sensitive signaling pathways. APE/Ref-1 is a multifunctional protein that serves as a redox chaperone that regulates many nuclear transcription factors and is an important mechanism in cancer cell survival of oxidative stress. Previous studies showed that APE/Ref-1 is a potential druggable target for melanoma therapy. In this study, we synthesized a novel APE/Ref-1 inhibitor, bis-cinnamoyl-1,12-dodecamethylenediamine (2). In a xenograft mouse model, compound 2 treatment (5 mg/kg) significantly inhibited tumor growth compared to the control group, with no significant systemic toxicity observed We further synthesized compound 2 analogs to determine the structure-activity relationship based on their anti-melanoma activities. Among those, 4-hydroxyphenyl derivative (11) exhibited potent anti-melanoma activities and improved water solubility compared to its parental compound 2. The IC50 of compound 11 was found to be less than 0.1 μM. Compared to other known APE/Ref-1 inhibitors, compound 11 exhibited increased potency in inhibiting melanoma proliferation. As determined by luciferase reporter analyses, compound 2 was shown to effectively inhibit H2O2-activated AP-1 transcription activities. Targeting APE/Ref-1-mediated signaling using pharmaceutical inhibitors is a novel and effective strategy for melanoma treatment with potentially high impact.

Molecules published new progress about Activator protein 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 17082-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C9H7ClO, Quality Control of 17082-09-6.

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

Dejouy, Garance; Renault, Kevin; Bonnin, Quentin; Chevalier, Arnaud; Michaudet, Cedric; Picquet, Michel; Valverde, Ibai E.; Romieu, Anthony published the artcile< Fluorogenic Enzyme-Triggered Domino Reactions Producing Quinoxalin-2(1H)-one-based Heterocycles>, Synthetic Route of 27841-33-4, the main research area is fluorogenic quinoxalin heterocycle enzyme triggered.

A simple and effective biocompatible domino reaction triggered by a model protease and leading to the formation of strongly fluorescent quinoxalin-2(1H)-one N-heterocycles is described. Some pos. attributes including versatility and the ability to provide outstanding fluorescence “”OFF-ON”” responses were revealed by this work. They open the way for practical applications of this novel type of “”covalent-assembly””-based fluorescent probe in the fields of sensing and bioimaging.

Organic Letters published new progress about Confocal microscopy. 27841-33-4 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H12N2O2, Synthetic Route of 27841-33-4.

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

Stafford, Alex; Ahn, Dowon; Raulerson, Emily K.; Chung, Kun-You; Sun, Kaihong; Cadena, Danielle M.; Forrister, Elena M.; Yost, Shane R.; Roberts, Sean T.; Page, Zachariah A. published the artcile< Catalyst Halogenation Enables Rapid and Efficient Polymerizations with Visible to Far-Red Light>, Formula: C4H4ClNO2, the main research area is catalyst halogenation rapid polymerization visible Far Red light; high resolution visible light 3D printing.

The driving of rapid polymerizations with visible to near-IR light will enable nascent technologies in the emerging fields of bio- and composite-printing. However, current photopolymerization strategies are limited by long reaction times, high light intensities, and/or large catalyst loadings. The improvement of efficiency remains elusive without a comprehensive, mechanistic evaluation of photocatalysis to better understand how composition relates to polymerization metrics. With this objective in mind, a series of methine- and aza-bridged boron dipyrromethene (BODIPY) derivatives were synthesized and systematically characterized to elucidate key structure-property relationships that facilitate efficient photopolymerization driven by visible to far-red light. For both BODIPY scaffolds, halogenation was shown as a general method to increase polymerization rate, quant. characterized using a custom real-time IR spectroscopy setup. Furthermore, a combination of steady-state emission quenching experiments, electronic structure calculations, and ultrafast transient absorption revealed that efficient intersystem crossing to the lowest excited triplet state upon halogenation was a key mechanistic step to achieving rapid photopolymerization reactions. Unprecedented polymerization rates were achieved with extremely low light intensities (<1 mW/cm2) and catalyst loadings (<50 μM), exemplified by reaction completion within 60 s of irradiation using green, red, and far-red light-emitting diodes. Halogenated BODIPY photoredox catalysts were addnl. employed to produce complex 3D structures using high-resolution visible light 3D printing, demonstrating the broad utility of these catalysts in additive manufacturing Journal of the American Chemical Society published new progress about Attenuated-total-reflectance IR spectroscopy. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Formula: C4H4ClNO2.

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