Month: October 2022

Tang, Ke; Roca, Jorjethe; Chen, Rong; Ansari, Anjum; Liang, Jie published the artcile< Thermodynamics of unfolding mechanisms of mouse mammary tumor virus pseudoknot from a coarse-grained loop-entropy model>, Category: imidazoles-derivatives, the main research area is mammary tumor virus pseudoknot thermodn entropy model; Energy landscape; Fluorescence spectroscopy; Heat capacity; Loop entropy; PK3D; Pseudoknotted RNA; RNA folding; RNA hairpin; Unfolding mechanism.

Pseudoknotted RNA mols. play important biol. roles that depend on their folded structure. To understand the underlying principles that determine their thermodn. and folding/unfolding mechanisms, we carried out a study on a variant of the mouse mammary tumor virus pseudoknotted RNA (VPK), a widely studied model system for RNA pseudoknots. Our method is based on a coarse-grained discrete-state model and the algorithm of PK3D (pseudoknot structure predictor in three-dimensional space), with RNA loops explicitly constructed and their conformational entropic effects incorporated. Our loop entropy calculations are validated by accurately capturing previously measured melting temperatures of RNA hairpins with varying loop lengths. For each of the hairpins that constitutes the VPK, we identified alternative conformations that are more stable than the hairpin structures at low temperatures and predicted their populations at different temperatures Our predictions were validated by thermodn. experiments on these hairpins. We further computed the heat capacity profiles of VPK, which are in excellent agreement with available exptl. data. Notably, our model provides detailed information on the unfolding mechanisms of pseudoknotted RNA. Anal. of the distribution of base-pairing probability of VPK reveals a cooperative unfolding mechanism instead of a simple sequential unfolding of first one stem and then the other. Specifically, we find a simultaneous “”loosening”” of both stems as the temperature is raised, whereby both stems become partially melted and co-exist during the unfolding process.

Journal of Biological Physics published new progress about Algorithm. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wang, Kai-Bo; Dickerhoff, Jonathan; Wu, Guanhui; Yang, Danzhou published the artcile< PDGFR-β Promoter Forms a Vacancy G-Quadruplex that Can Be Filled in by dGMP: Solution Structure and Molecular Recognition of Guanine Metabolites and Drugs>, Safety of 7H-Purin-2-amine, the main research area is vacancy G quadruplex PDGFRbeta promoter dGMP conformation guanine drug.

Aberrant expression of PDGFR-β is associated with a number of diseases. The G-quadruplexes (G4s) formed in PDGFR-β gene promoter are transcriptional modulators and amenable to small mol. targeting. The major G4 formed in the PDGFR-β gene promoter was previously shown to have a broken G-strand. Herein, we report that the PDGFR-β gene promoter sequence forms a vacancy G-quadruplex (vG4) which can be filled in and stabilized by physiol. relevant guanine metabolites, such as dGMP, GMP, and cGMP, as well as guanine-derivative drugs. We determined the NMR structure of the dGMP-fill-in PDGFR-β vG4 in K+ solution This is the first structure of a guanine-metabolite-fill-in vG4 based on a human gene promoter sequence. Our structure and systematic anal. elucidate the contributions of Hoogsten hydrogen bonds, sugar, and phosphate moieties to the specific G-vacancy fill-in. Intriguingly, an equilibrium of 3′- and 5′-end vG4s is present in the PDGFR-β promoter sequence, and dGMP favors the 5′-end fill-in. Guanine metabolites and drugs were tested and showed a conserved selectivity for the 5′-vacancy, except for cGMP. CGMP binds both the 3′- and 5′-end vG4s and forms two fill-in G4s with similar population. Significantly, guanine metabolites are involved in many physiol. and pathol. processes in human cells; thus, our results provide a structural basis to understand their potential regulatory functions by interaction with promoter vG4s. Moreover, the NMR structure can guide rational design of ligands that target the PDGFR-β vG4.

Journal of the American Chemical Society published new progress about Drugs. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Safety of 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Petrov, Viacheslav A.; Marshall, Will; Dooley, Rebecca published the artcile< One step synthesis of 1,3-dihydro-1-alkyl(aryl)-3-(hexafluoro-iso-propyl)-2H-imidazole-2-thiones>, Name: 5-Bromo-1-methyl-1H-imidazole, the main research area is tetrakistrifluoromethyldithietane reaction imidazole alkyl aryl; dithietane tetrakistrifluoromethyl reaction imidazole alkyl aryl; imidazolethione hexafluoroisopropyl preparation.

The reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (I) with variety of 1-alkyl- or 1-arylimidazoles led to the unexpected formation of 1,3-dihydro-1-alkyl(aryl)-3-(hexafluoroisopropyl)-2H-imidazole-2-thiones in 11-88% yields. The reaction proceeds in polar solvents such as DMF or DMSO leading to selective formation of the corresponding thiones which provide a simple one-step process for the preparation of these materials. While 1-alkylimidazoles rapidly react with I at ambient temperature, the reaction of 1-aryl- and 1-fluoralkylimidazoles requires higher temps and longer reaction times. Substituents in the 5-position of the imidazole ring hinder the reaction, but introduction of Me or Ph groups in the 5-position of imidazole totally blocked the formation of the corresponding thiones.

Journal of Fluorine Chemistry published new progress about Crystal structure. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Name: 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Pilette, Charles published the artcile< Role of exosomes in allergic asthma: Signaling platforms between the epithelium and type 2 immunity>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is exosome allergic asthma signaling epithelium immunity; Asthma; Notch; contactin-1; type 2 immunity.

Exosomes activate (and are uptaken by) monocyte-derived, inflammatory dendritic cells (DCs) through contactin-1 and Notch2 activation, which in turn promotes TH2 cell-and TH17 cell-polarized immune activation along with mucus production and smooth muscle hyperresponsiveness. Airway epithelial cells release increased numbers of CD631 and CD811 exosomes following stimulation by house dust mite (HDM), a major allergen in allergic airway diseases such as rhinitis and asthma, and that those exosomes are also released in the bronchoalveolar lavage fluid from HDM-exposed mice. To address the role of these exosomes in the pathophysiol. of asthma, exosomes’ release by using GW4869, a noncompetitive inhibitor blocking exosome synthesis and/or release, which resulted in reduced recruitment of eosinophils in the bronchoalveolar lavage fluid from HDM-exposed and HDM-challenged mice. Airway tissue infiltration by inflammatory cells, mucus production, and levels of type 2 cytokines (IL-4, IL-5, and IL-13), as well as IFN-g levels but not IL-17A levels, were also downregulated.

Journal of Allergy and Clinical Immunology published new progress about Allergic asthma. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Schmitt, Christian; Kail, Dagmar; Mariano, Marica; Empting, Martin; Weber, Nadja; Paul, Tamara; Hartmann, Rolf W.; Engel, Matthias published the artcile< Design and synthesis of a library of lead-like 2,4-bisheterocyclic substituted thiophenes as selective Dyrk/Clk inhibitors>, Product Details of C4H5BrN2, the main research area is drug design bisheterocyclic thiophene Dyrk Clk inhibitor.

The Dyrk family of protein kinases is implicated in the pathogenesis of several diseases, including cancer and neurodegeneration. Pharmacol. inhibitors were mainly described for Dyrk1A so far, but in fewer cases for Dyrk1B, Dyrk2 or other isoforms. Herein, we report the development and optimization of 2,4-bisheterocyclic substituted thiophenes as a novel class of Dyrk inhibitors. The optimized hit compounds displayed favorable pharmacokinetic properties and high ligand efficiencies, and inhibited Dyrk1B in intact cells. In a larger selectivity screen, only Clk1 and Clk4 were identified as addnl. targets of compound 48, but no other kinases frequently reported as off-targets. Interestingly, Dyrk1A is implicated in the regulation of alternative splicing, a function shared with Clk1/Clk4; thus, some of the dual inhibitors might be useful as efficient splicing modulators. A further compound (29) inhibited Dyrk1A and 1B with an IC50 of 130 nM, showing a moderate selectivity over Dyrk2. Since penetration of the central nervous system (CNS) seems possible based on the physicochem. properties, this compound might serve as a lead for the development of potential therapeutic agents against glioblastoma. Furthermore, an inhibitor selective for Dyrk2 (24) was also identified, which might be are suitable as a pharmacol. tool to dissect Dyrk2 isoform-mediated functions.

PLoS One published new progress about Cell proliferation. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Product Details of C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Desage-El Murr, Marine; Cano, Celine; Golding, Bernard T.; Hardcastle, Ian R.; Hummersome, Marc; Frigerio, Mark; Curtin, Nicola J.; Menear, Keith; Richardson, Caroline; Smith, Graeme C. M.; Griffin, Roger J. published the artcile< 8-Biarylchromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK)>, Computed Properties of 1003-21-0, the main research area is biarylchromenone preparation inhibitor DNA dependent protein kinase; chromenone biaryl preparation inhibitor DNA dependent protein kinase.

The synthesis and biol. evaluation of libraries of 8-biarylchromen-4-ones enabled the elucidation of structure-activity relationships for inhibition of the DNA-dependent protein kinase (DNA-PK), with 8-(3-(thiophen-2-yl)phenyl)chromen-4-one and 8-(3-(thiophen-3-yl)phenyl)chromen-4-one being especially potent inhibitors.

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

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Li, Xiang; Chen, Zhipeng; Ni, Yaojun; Bian, Chengyu; Huang, Jingjing; Chen, Liang; Xie, Xueying; Wang, Jun published the artcile< Tumor-associated macrophages secret exosomal miR-155 and miR-196a-5p to promote metastasis of non-small-cell lung cancer>, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is tumor associated macrophage mir155 transcriptome lung cancer metastasis; Tumor-associated macrophages (TAMs); epithelial-mesenchymal transition (EMT); exosomes; miR-155; miR-196a-5p; non-small-cell lung cancer (NSCLC).

Understanding the mol. basis underlying metastasis of non-small cell lung cancer (NSCLC) may provide a new therapeutic modality for the treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis remain undefined. In this study, we aimed to discover a novel regulatory pathway involved in NSCLC metastasis. Cell Counting Kit-8 (CCK-8), Transwell, western blot assays were used to assess cell viability, migration, invasion and epithelial-mesenchymal transition (EMT). Exosomes from macrophages medium were characterized, and in vitro cell coculture was further conducted to investigate M2 derived exosomes mediated crosstalk between TAMs and tumor cells. Besides, miRNA microarray was used to analyze miRNA expression profiles of M0 and M2 derived exosomes. Luciferase reporter assay was used to verify the potential binding between miRNA and mRNA. Moreover, 6-wk-old male BALB/c nude mice were performed to establish transplantation tumor model using tail vein injection. Hematoxylin & eosin staining was used to detect the metastasis of tumor tissues. We found that M2 TAMs were the main TAMs in metastatic tissues of NSCLC patients and exosomes derived from M2 TAMs were able to promote cell viability, cell migration, cell invasion and EMT in NSCLC. We demonstrated that miR-155 and miR-196a-5p were abundant in M2 TAMs and exosomes secreted by M2 TAMs. Functional experiments demonstrated that the deletion of miR-155 and miR-196a-5p in M2 TAMs significantly prevented NSCLC metastasis in vitro and in vivo. To clarify the mechanism governing miR-155 and miR-196a-5p from M2 TAMs, we carried out bioinformatics anal. to predict potential target genes. Mechanistically, miR-155 and miR-196a-5p directly bound to the 3′-UTR of Ras association domain family member 4 (RASSF4), and neg. regulating RASSF4 expression. At last, rescue assays demonstrated that miR-155 and miR-196a-5p exerted its performance by RASSF4. Overall, we revealed a new regulatory pathway that was M2 TAMs secreted exosomal miR-155 and miR-196a-5p to promote NSCLC metastasis. This dynamic and reciprocal cross-talk between NSCLC and macrophages innovatively provided a potential opportunity for diagnosis and treatment of NSCLC.

Translational Lung Cancer Research published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (BCAT1). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

D’Souza, Sara; Miller, Justin E.; Ahn, Jenny; Subandi, Raechel; Lozano, Daniel; Ramirez, James; Goff, Marisa; Davidian, Christina; Miller, Jeffrey H. published the artcile< The antibiotic trimethoprim displays strong mutagenic synergy with 2-aminopurine>, Name: 7H-Purin-2-amine, the main research area is antibiotic; mutagenesis; synergy; trimethoprim.

We show that trimethoprim (TMP), an antibiotic in current use, displays a strong synergistic effect on mutagenesis in Escherichia coli when paired with the base analog 2-aminopurine (2AP), resulting in a 35-fold increase in mutation frequencies in the rpoB-Rifr system. Combination therapies are often employed both as antibiotic treatments and in cancer chemotherapy. However, mutagenic effects of these combinations are rarely examined An anal. of the mutational spectra of TMP, 2AP, and their combination indicates that together they trigger a response via an alteration in deoxynucleoside triphosphate (dNTP) ratios that neither compound alone can trigger. A similar, although less strong, response is seen with the frameshift mutagen ICR191 and 2AP. These results underscore the need for testing the effects on mutagenesis of combinations of antibiotics and chemotherapeutics.

Antimicrobial Agents and Chemotherapy published new progress about 452-06-2. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Name: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Boehnke, Hendrik; Roettger, Katharina; Ingle, Rebecca A.; Marroux, Hugo J. B.; Bohnsack, Mats; Schwalb, Nina K.; Orr-Ewing, Andrew J.; Temps, Friedrich published the artcile< Electronic Relaxation Dynamics of UV-Photoexcited 2-Aminopurine-Thymine Base Pairs in Watson-Crick and Hoogsteen Conformations>, Electric Literature of 452-06-2, the main research area is electronic relaxation dynamics UV photoexcited aminopurine thymine base conformation.

The fluorescent analog 2-aminopurine (2AP) of the canonical nucleobase adenine (6-aminopurine) base-pairs with thymine (T) without disrupting the helical structure of DNA. It therefore finds frequent use in mol. biol. for probing DNA and RNA structures and conformational dynamics. However, detailed understanding of the processes responsible for fluorescence quenching remains largely elusive on a fundamental level. Although attempts have been made to ascribe decreased excited-state lifetimes to intrastrand charge-transfer and stacking interactions, possible influences from dynamic interstrand H-bonding have been widely ignored. Here, we investigate the electronic relaxation of UV-excited 2AP·T in Watson-Crick (WC) and Hoogsteen (HS) conformations. Although the WC conformation features slowed-down, monomer-like electronic relaxation in τ ∼ 1.6 ns toward ground-state recovery and triplet formation, the dynamics associated with 2AP·T in the HS motif exhibit faster deactivation in τ ∼ 70 ps. As recent research has revealed abundant transient interstrand H-bonding in the Hoogsteen motif for duplex DNA, the established model for dynamic fluorescence quenching may need to be revised in the light of our results. The underlying supramol. photophys. mechanisms are discussed in terms of a proposed excited-state double-proton transfer as an efficient deactivation channel for recovery of the HS species in the electronic ground state.

Journal of Physical Chemistry B published new progress about Double-stranded DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Electric Literature of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ambati, Srinivasa Rao; Patel, Jeevan Lal; Chandrakar, Komal; Sarkar, Uttam; Penta, Santhosh; Banerjee, Subhash; Varma, Rajender S. published the artcile< One-pot, three-component synthesis of novel coumarinyl-pyrazolo[3,4-b]pyridine-3-carboxylate derivatives using [AcMIm]FeCl4 as recyclable catalyst>, Application of C6H9ClN2O2, the main research area is benzylhydrazine cyano hydroxyacrylate coumarinyl acrylaldehyde ionic liquid multicomponent reaction; benzyl coumarinyl pyrazolopyridine carboxylate preparation green chem.

Multicomponent synthesis of novel coumarin-based fused pyrazolo[3,4-b]pyridine-3-carboxylate derivatives I [R = H, OH, F, CN; R1 = Me, Et, i-Pr, t-Bu; R2 = H, MeO, Br] was developed using acidic ionic liquid, 1-acyl-3-methylimidazolium tetrachloroferrate ([AcMIm]FeCl4) under mild and environmentally benign reaction conditions. The prepared [AcMIm]FeCl4 served as a catalyst as well as the reaction medium and was reused for at least four times without significant loss of yield. The ensuing compounds, I were identified by FT-IR, 1H NMR and 13C NMR and mass spectroscopic studies. The developed method offers several advantages such as a simple protocol, excellent yields of the products (90-92%), shorter reaction time (2 h), recyclability of the catalyst, eco-friendly reaction conditions and better values of green chem. metrics like low E factor (0.32), high reaction mass efficiency (75.28%), low process mass efficiency (1.32) and high atom economy (81.82).

Journal of Molecular Structure published new progress about Aliphatic acids, esters Role: SPN (Synthetic Preparation), PREP (Preparation). 700370-07-6 belongs to class imidazoles-derivatives, and the molecular formula is C6H9ClN2O2, Application of C6H9ClN2O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem