Category: imidazoles-derivatives

Cristofalo, Matteo; Kovari, Daniel; Corti, Roberta; Salerno, Domenico; Cassina, Valeria; Dunlap, David; Mantegazza, Francesco published the artcile< Nanomechanics of Diaminopurine-Substituted DNA>, Related Products of 452-06-2, the main research area is diaminopurine double strand DNA nanomechanics.

2,6-Diaminopurine (DAP) is a nucleobase analog of adenine. When incorporated into double-stranded DNA (dsDNA), it forms three hydrogen bonds with thymine. Rare in nature, DAP substitution alters the phys. characteristics of a DNA mol. without sacrificing sequence specificity. Here, we show that in addition to stabilizing double-strand hybridization, DAP substitution also changes the mech. and conformational properties of dsDNA. Thermal melting experiments reveal that DAP substitution raises melting temperatures without diminishing sequence-dependent effects. Using a combination of at. force microscopy (AFM), magnetic tweezer (MT) nanomech. assays, and CD spectroscopy, we demonstrate that DAP substitution increases the flexural rigidity of dsDNA yet also facilitates conformational shifts, which manifest as changes in mol. length. DAP substitution increases both the static and dynamic persistence length of DNA (measured by AFM and MT, resp.). In the static case (AFM), in which tension is not applied to the mol., the contour length of DAP-DNA appears shorter than wild-type (WT)-DNA; under tension (MT), they have similar dynamic contour lengths. At tensions above 60 pN, WT-DNA undergoes characteristic overstretching because of strand separation (tension-induced melting) and spontaneous adoption of a conformation termed S-DNA. Cyclic overstretching and relaxation of WT-DNA at near-zero loading rates typically yields hysteresis, indicative of tension-induced melting; conversely, cyclic stretching of DAP-DNA showed little or no hysteresis, consistent with the adoption of the S-form, similar to what has been reported for GC-rich sequences. However, DAP-DNA overstretching is distinct from GC-rich overstretching in that it happens at a significantly lower tension. In physiol. salt conditions, evenly mixed AT/GC DNA typically overstretches around 60 pN. GC-rich sequences overstretch at similar if not slightly higher tensions. Here, we show that DAP-DNA overstretches at 52 pN. In summary, DAP substitution decreases the overall stability of the B-form double helix, biasing toward non-B-form DNA helix conformations at zero tension and facilitating the B-to-S transition at high tension.

Biophysical Journal published new progress about Conformational transition. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Related Products of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Chen, Hu; Lei, Min; Hu, Lihong published the artcile< Synthesis of 1-aryl indoles via coupling reaction of indoles and aryl halides catalyzed by CuI/metformin>, Product Details of C4H5BrN2, the main research area is aryl indole preparation; Ullmann coupling indole aryl halide copper metformin catalyst.

Ullmann-type C-N coupling reaction has been developed for the synthesis of 1-aryl indole derivatives by indoles and aryl halides in the presence of CuI/metformin (CuI/Met) in DMF. This method is very easy, rapid, and high yielding reaction for the synthesis of 1-aryl indoles. In particular, the metformin, which is used as ligand, is inexpensive and nontoxic that is considered to be relatively environmentally benign.

Tetrahedron published new progress about Aryl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Product Details of C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhang, Patricia; Le, Chi “Chip”; MacMillan, David W. C. published the artcile< Silyl Radical Activation of Alkyl Halides in Metallaphotoredox Catalysis: A Unique Pathway for Cross-Electrophile Coupling>, Application In Synthesis of 1003-21-0, the main research area is alkyl halide coupling reaction aryl bromide metallaphotoredox catalyst tristrimethylsilylsilane.

A strategy for cross-electrophile coupling has been developed via the merger of photoredox and transition metal catalysis. In this report, we demonstrate the use of com. available tris(trimethylsilyl)silane with metallaphotoredox catalysis to efficiently couple alkyl bromides with aryl or heteroaryl bromides in excellent yields. We hypothesize that a photocatalytically generated silyl radical species can perform halogen-atom abstraction to activate alkyl halides as nucleophilic cross-coupling partners. This protocol allows the use of mild yet robust conditions to construct Csp3-Csp2 bonds generically via a unique cross-coupling pathway.

Journal of the American Chemical Society published new progress about Aryl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Application In Synthesis of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tanis, Virginia M.; Venkatesan, Hariharan; Cummings, Maxwell D.; Albers, Michael; Kent Barbay, J.; Herman, Krystal; Kummer, David A.; Milligan, Cynthia; Nelen, Marina I.; Nishimura, Rachel; Schlueter, Thomas; Scott, Brian; Spurlino, John; Wolin, Ronald; Woods, Craig; Xue, Xiaohua; Edwards, James P.; Fourie, Anne M.; Leonard, Kristi published the artcile< 3-Substituted Quinolines as RORγt Inverse Agonists>, Quality Control of 1003-21-0, the main research area is quinoline derivative preparation ROR gamma t inverse agonist SAR; IL-17; Inverse agonist; RORγt; Retinoic acid-related orphan nuclear receptor gamma t; Th17.

We have previously reported the syntheses of a series of 3,6-disubstituted quinolines as modulators of the retinoic acid receptor-related orphan receptor gamma t (RORγt). These mols. are potent binders but are high mol. weight and they exhibited poor solubility at pH 2 and pH 7. This manuscript details our efforts at improving phys. chem. properties for this series of compounds by increasing the diversity at the 3-position (i.e. introducing heteroatoms and lowering the mol. weight). These efforts have led to mols. which are potent binders with improved solubility

Bioorganic & Medicinal Chemistry Letters published new progress about Drug design. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Quality Control of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Schroeder, Griffin M.; Dutta, Debapratim; Cavender, Chapin E.; Jenkins, Jermaine L.; Pritchett, Elizabeth M.; Baker, Cameron D.; Ashton, John M.; Mathews, David H.; Wedekind, Joseph E. published the artcile< Analysis of a preQ1-I riboswitch in effector-free and bound states reveals a metabolite-programmed nucleobase-stacking spine that controls gene regulation>, Recommanded Product: 7H-Purin-2-amine, the main research area is turnip yellow mosaic virus preQ1I riboswitch nucleobase gene regulation.

Riboswitches are structured RNA motifs that recognize metabolites to alter the conformations of downstream sequences, leading to gene regulation. To investigate this mol. framework, we determined crystal structures of a preQ1-I riboswitch in effector-free and bound states at 2.00 Å and 2.65 Å-resolution Both pseudoknots exhibited the elusive L2 loop, which displayed distinct conformations. Conversely, the Shine-Dalgarno sequence (SDS) in the S2 helix of each structure remained unbroken. The expectation that the effector-free state should expose the SDS prompted us to conduct solution experiments to delineate environmental changes to specific nucleobases in response to preQ1. We then used nudged elastic band computational methods to derive conformational-change pathways linking the crystallog.-determined effector-free and bound-state structures. Pathways featured: (i) unstacking and unpairing of L2 and S2 nucleobases without preQ1-exposing the SDS for translation and (ii) stacking and pairing L2 and S2 nucleobases with preQ1-sequestering the SDS. Our results reveal how preQ1 binding reorganizes L2 into a nucleobase-stacking spine that sequesters the SDS, linking effector recognition to biol. function. The generality of stacking spines as conduits for effector-dependent, interdomain communication is discussed in light of their existence in adenine riboswitches, as well as the turnip yellow mosaic virus ribosome sensor.

Nucleic Acids Research published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Recommanded Product: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Angulo, Sandra; Morales, Albert; Danese, Silvio; Llacuna, Laura; Masamunt, Maria Carme; Pultz, Nicole; Cifone, Maria Grazia; De Simone, Claudio; Delgado, Salvadora; Vila, Jordi; Panes, Julian; Donskey, Curtis; Fernandez-Checa, Jose C.; Fiocchi, Claudio; Sans, Miquel published the artcile< Probiotic sonicates selectively induce mucosal immune cells apoptosis through ceramide generation via neutral sphingomyelinase>, Application In Synthesis of 6823-69-4, the main research area is NSMase mononuclear cell apoptosis ceramide probiotic lamina propria.

Background: Probiotics appear to be beneficial in inflammatory bowel disease, but their mechanism of action is incompletely understood. We investigated whether probiotic-derived sphingomyelinase mediates this beneficial effect. Methodol./Principal Findings: Neutral sphingomyelinase (NSMase) activity was measured in sonicates of the probiotic L. brevis (LB) and S. thermophilus (ST) and the non-probiotic E. coli (EC) and E. faecalis (EF). Lamina propria mononuclear cells (LPMC) were obtained from patients with Crohn’s disease (CD) and Ulcerative Colitis (UC), and peripheral blood mononuclear cells (PBMC) from healthy volunteers, analyzing LPMC and PBMC apoptosis susceptibility, reactive oxygen species (ROS) generation and JNK activation. In some experiments, sonicates were preincubated with GSH or GW4869, a specific NSMase inhibitor. NSMase activity of LB and ST was 10-fold that of EC and EF sonicates. LB and ST sonicates induced significantly more apoptosis of CD and UC than control LPMC, whereas EC and EF sonicates failed to induce apoptosis. Pre-stimulation with anti-CD3/CD28 induced a significant and time-dependent increase in LB-induced apoptosis of LPMC and PBMC. Exposure to LB sonicates resulted in JNK activation and ROS production by LPMC. NSMase activity of LB sonicates was completely abrogated by GW4869, causing a dose-dependent reduction of LB-induced apoptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. Conclusions: These results suggest that induction of immune cell apoptosis is a mechanism of action of some probiotics, and that NSMase-mediated ceramide generation contributes to the therapeutic effects of probiotics.

PLoS One published new progress about Apoptosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application In Synthesis of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Takenaga, Keizo; Koshikawa, Nobuko; Nagase, Hiroki published the artcile< Intercellular transfer of mitochondrial DNA carrying metastasis-enhancing pathogenic mutations from high- to low-metastatic tumor cells and stromal cells via extracellular vesicles>, Reference of 6823-69-4, the main research area is mtDNA stromal EV metastasis enhancing pathogenic mutation intercellular transfer; Extracellular vesicles; Intercellular transfer; Lung cancer; Metastasis; Mitochondria; Mitochondrial DNA; Mutation; Tumor microenvironment.

Mitochondrial DNA (mtDNA) carrying certain pathogenic mutations or single nucleotide variants (SNVs) enhances the invasion and metastasis of tumor cells, and some of these mutations are homoplasmic in tumor cells and even in tumor tissues. On the other hand, intercellular transfer of mitochondria and cellular components via extracellular vesicles (EVs) and tunneling nanotubes (TNTs) has recently attracted intense attention in terms of cell-to-cell communication in the tumor microenvironment. It remains unclear whether metastasisenhancing pathogenic mutant mtDNA in tumor cells is intercellularly transferred between tumor cells and stromal cells. In this study, we investigated whether mtDNA with the NADH dehydrogenase subunit 6 (ND6) G13997A pathogenic mutation in highly metastatic cells can be horizontally transferred to low-metastatic cells and stromal cells in the tumor microenvironment. When MitoTracker Deep Red-labeled high-metastatic Lewis lung carcinoma A11 cells carrying the ND6 G13997A mtDNA mutation were cocultured with Cell Light mitochondria-GFP-labeled low-metastatic P29 cells harboring wild-type mtDNA, bidirectional transfer of red- and green-colored vesicles, probably mitochondria-related EVs, was observed in a time-dependent manner. Similarly, intercellular transfer of mitochondria-related EVs occurred between A11 cells and α-smooth muscle actin (α-SMA)-pos. cancer-associated fibroblasts (CAFs, WA-mFib), macrophages (RAW264.7) and cytotoxic T cells (CTLL-2). Intercellular transfer was suppressed by inhibitors of EV release. The large and small EV fractions (L-EV and S-EV, resp.) prepared from the conditioned medium by differential ultracentrifugation both were found to contain mtDNA, although only S-EVs were efficiently incorporated into the cells. Several subpopulations had evidence of LC3-II and contained degenerated mitochondrial components in the S-EV fraction, signaling to the existence of autophagy-related S-EVs. Interestingly, the S-EV fraction contained a MitoTracker-pos. subpopulation, which was inhibited by the respiration inhibitor antimycin A, indicating the presence of mitochondria with membrane potential. It was also demonstrated that mtDNA was transferred into mtDNA-less ρ0 cells after coculture with the S-EV fraction. In syngeneic mouse s.c. tumors formed by a mixture of A11 and P29 cells, the mitochondria-related EVs released from A11 cells reached distantly positioned P29 cells and CAFs. These results suggest that metastasis-enhancing pathogenic mtDNA derived from metastatic tumor cells is transferred to low-metastatic tumor cells and stromal cells via S-EVs in vitro and in the tumor microenvironment, inferring a novel mechanism of enhancement of metastatic potential during tumor progression.

BMC Molecular and Cell Biology published new progress about Animal gene, ND1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhu, Jinbo; Yan, Zhiqiang; Boskovic, Filip; Haynes, Cally J. E.; Kieffer, Marion; Greenfield, Jake L.; Wang, Jin; Nitschke, Jonathan R.; Keyser, Ulrich F. published the artcile< FeII4L4 tetrahedron binds and aggregates DNA Gquadruplexes>, Product Details of C5H5N5, the main research area is iron ligand tetrahedron metal organic cage DNA G quadruplex.

Since the discovery of the G-quadruplex (G4) structure in telomeres in 1980s, studies have established the role it plays in various biol. processes. Here we report binding between DNA G4 and a self-assembled tetrahedral metal-organic cage 1 and consequent formation of aggregates, whereby the cage protects the DNA G4 from cleavage by S1 nuclease. We monitor DNA-cage interaction using fluorescence spectroscopy, firstly by quenching of a fluorescent label appended to the 5′ end of G4. Secondly, we detect the decrease in fluorescence of the G4-selective dyes thioflavin-T and Zn-PPIX bound to various DNA G4 sequences following the addition of cage 1. Our results demonstrate that 1 interacts with a wide range of G4s. Moreover, gel electrophoresis, CD and dynamic light scattering measurements establish the binding of 1 to G4 and indicate the formation of aggregate structures. Finally, we find that DNA G4 contained in an aggregate of cage 1 is protected from cleavage by S1 nuclease.

Chemical Science published new progress about Absorption spectra. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Product Details of C5H5N5.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ling, Irene; Sobolev, Alexandre N.; Dalgarno, Scott J. published the artcile< Inclusion complexes of imidazolium carboxylate-metal species in the water-soluble sulfonated calix[4]arene system>, Computed Properties of 700370-07-6, the main research area is preparation imidazolium carboxylate metal water sulfonated calixarene inclusion complex; crystal structure imidazolium carboxylate metal sulfonated calixarene inclusion complex.

Two multi-component crystal structures comprising a carboxylic acid-functionalized imidazolium zwitterion, a p-sulfonatocalix[4]arene anion and aquated metal ion (Na+ or Y3+) with or without an auxiliary component (the 3-methoxyphenyl-triphenylphosphonium cation) are reported. The carboxylic acid-functionalized imidazolium ion binds either as a monodentate or a bidentate ligand depending on the nature of the metal ions, and a bi-layer arrangement prevails in the extended structure regardless of the type of metal ion employed or presence/lack of auxiliary component.

Journal of Coordination Chemistry published new progress about Crystal structure. 700370-07-6 belongs to class imidazoles-derivatives, and the molecular formula is C6H9ClN2O2, Computed Properties of 700370-07-6.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Yang, Qianxi; Zhao, Shaorong; Shi, Zhendong; Cao, Lixia; Liu, Jingjing; Pan, Teng; Zhou, Dongdong; Zhang, Jin published the artcile< Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling>, Reference of 6823-69-4, the main research area is chemotherapy miR378a3p miR378d EZH2 STAT3 signaling breast cancer; Cancer stemness; Chemotherapy resistance; Chemotherapy-elicited exosomes; miR-378a-3p; miR-378d.

Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathol. complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood. Using com. kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population anal. and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs. Here, we provide clin. evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome-induced drug resistance in a nude mouse tumor xenograft model. This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of the WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.

Journal of Experimental & Clinical Cancer Research published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (3′-UTR). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem