Month: October 2022

Ansideri, Francesco; Macedo, Joana T.; Eitel, Michael; El-Gokha, Ahmed; Zinad, Dhafer S.; Scarpellini, Camilla; Kudolo, Mark; Schollmeyer, Dieter; Boeckler, Frank M.; Blaum, Baerbel S.; Laufer, Stefan A.; Koch, Pierre published the artcile< Structural Optimization of a Pyridinylimidazole Scaffold: Shifting the Selectivity from p38α Mitogen-Activated Protein Kinase to c-Jun N-Terminal Kinase 3>, Category: imidazoles-derivatives, the main research area is pyridinylimidazole preparation JNK3 inhibitor p38alpha MAP kinase.

Starting from known p38α mitogen-activated protein kinase (MAPK) inhibitors, a series of inhibitors of the c-Jun N-terminal kinase (JNK) 3 was obtained. Altering the substitution pattern of the pyridinylimidazole scaffold proved to be effective in shifting the inhibitory activity from the original target p38α MAPK to the closely related JNK3. In particular, a significant improvement for JNK3 selectivity could be achieved by addressing the hydrophobic region I with a small Me group. Furthermore, addnl. structural modifications permitted to explore structure-activity relationships. The most potent inhibitor 4-(4-methyl-2-(methylthio)-1H-imidazol-5-yl)-N-(4-morpholinophenyl)pyridin-2-amine showed an IC50 value for the JNK3 in the low triple digit nanomolar range and its binding mode was confirmed by x-ray crystallog.

ACS Omega published new progress about Bioactive lead compounds. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Bhat, Owais M.; Li, Guangbi; Yuan, Xinxu; Huang, Dandan; Gulbins, Erich; Kukreja, Rakesh C.; Li, Pin-Lan published the artcile< Arterial Medial Calcification through Enhanced small Extracellular Vesicle Release in Smooth Muscle-Specific Asah1 Gene Knockout Mice>, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is arterial medial calcification Asah1 small extracellular vesicle smooth muscle.

Arterial medial calcification (AMC) involves an increased small extracellular vesicle (sEV) secretion and apatite calcium precipitation in the arterial wall. The mechanisms mediating AMC remain poorly understood. In the present study, smooth muscle-specific acid ceramidase (Ac) gene knockout mice (Asah1fl/fl/SMCre) were used to demonstrate the role of lysosomal ceramide signaling pathway in AMC. Asah1fl/fl/SMCre mice were found to have more severe AMC in both aorta and coronary arteries compared to their littermates (Asah1fl/fl/SMwt and WT/WT mice) after receiving a high dose vitamin D. These mice also had pronounced upregulation of osteopontin and RUNX2 (osteogenic markers), CD63, AnX2 (sEV markers) and ALP expression (mineralization marker) in the arterial media. In cultured coronary arterial smooth muscle cells (CASMCs) from Asah1fl/fl/SMCre mice, high dose of Pi led to a significantly increased calcium deposition, phenotypic change and sEV secretion compared to WT CASMCs, which was associated with reduced lysosome-multivesicular body (MVB) interaction. Also, GW4869, sEV release inhibitor decreased sEV secretion and calcification in these cells. Lysosomal transient receptor potential mucolipin 1 (TRPML1) channels regulating lysosome interaction with MVBs were found remarkably inhibited in Asah1fl/fl/SMCre CASMCs as shown by GCaMP3 Ca2+ imaging and Port-a-Patch patch clamping of lysosomes. Lysosomal Ac in SMCs controls sEV release by regulating lysosomal TRPML1 channel activity and lysosome-MVB interaction, which importantly contributes to phenotypic transition and AMC.

Scientific Reports published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (Asah1). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tan, Ying; You, Changjun; Park, Jiyeong; Kim, Hyun Suk; Guo, Su; Scharer, Orlando D.; Wang, Yinsheng published the artcile< Transcriptional Perturbations of 2,6-Diaminopurine and 2-Aminopurine>, Recommanded Product: 7H-Purin-2-amine, the main research area is transcription diaminopurine aminopurine.

2,6-Diaminopurine (Z) is a naturally occurring adenine (A) analog that bacteriophages employ in place of A in their genetic alphabet. Recent discoveries of biogenesis pathways of Z in bacteriophages have stimulated substantial research interest in this DNA modification. Here, the authors systematically examined the effects of Z on the efficiency and fidelity of DNA transcription. The authors’ results showed that Z exhibited no mutagenic yet substantial inhibitory effects on transcription mediated by purified T7 RNA polymerase and by human RNA polymerase II in HeLa nuclear extracts and in human cells. A structurally related adenine analog, 2-aminopurine (2AP), strongly blocked T7 RNA polymerase but did not impede human RNA polymerase ii in vitro or in human cells, where no mutant transcript could be detected. The lack of mutagenic consequence and the presence of a strong blockage effect of Z on transcription suggest a role of Z in transcriptional regulation. Z is also subjected to removal by transcription-coupled nucleotide-excision repair (TC-NER), but not global-genome NER in human cells. The authors’ findings provide new insight into the effects of Z on transcription and its potential biol. functions.

ACS Chemical Biology published new progress about Homo sapiens. 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

Ohba, Masashi; Mukaihira, Takafumi; Fujii, Tozo published the artcile< Synthesis of 5-arylthio-3-methyl-L-histidine, a model for the starfish alkaloid imbricatine>, Electric Literature of 1003-21-0, the main research area is histidine arylthiomethyl; imbricatine model synthesis.

Syntheses of 3-methyl-5-phenylthio-L-histidine (I, R = Ph) and 3-methyl-5-(1-naphthyl)thio-L-histidine ( R = 1-naphthyl), selected as models for the asteroid alkaloid imbricatine (II), have now become feasible through a 10-step route starting from 4(5)-bromoimidazole. The key steps involve replacement of the 4-bromo group by an arylthio group in the aldehyde III and construction of the L-alanine moiety in the chlorides IV by the “”bis-lactim ether”” method.

Heterocycles published new progress about 1003-21-0. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Electric Literature of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Chen, Jianzhong; Wang, Xingyu; Pang, Laixue; Zhang, John Z. H.; Zhu, Tong published the artcile< Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations>, Related Products of 452-06-2, the main research area is guanine riboswitch mutation ligand binding mol dynamics simulation.

Riboswitches can regulate gene expression by direct and specific interactions with ligands and have recently attracted interest as potential drug targets for antibacterial. In this work, mol. dynamics (MD) simulations, free energy perturbation (FEP) and mol. mechanics generalized Born surface area (MM-GBSA) methods were integrated to probe the effect of mutations on the binding of ligands to guanine riboswitch (GR). The results not only show that binding free energies predicted by FEP and MMGBSA obtain an excellent correlation, but also indicate that mutations involved in the current study can strengthen the binding affinity of ligands GR. Residue-based free energy decomposition was applied to compute ligand-nucleotide interactions and the results suggest that mutations highly affect interactions of ligands with key nucleotides U22, U51 and C74. Dynamics analyses based on MD trajectories indicate that mutations not only regulate the structural flexibility but also change the internal motion modes of GR, especially for the structures J12, J23 and J31, which implies that the aptamer domain activity of GR is extremely plastic and thus readily tunable by nucleotide mutations. This study is expected to provide useful mol. basis and dynamics information for the understanding of the function of GR and possibility as potential drug targets for antibacterial.

Nucleic Acids Research published new progress about Free energy of binding. 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

Sui, Xintong; Liu, Wei; Liu, Zhi published the artcile< Exosomes derived from LPS-induced MHs cells prompted an inflammatory response in sepsis-induced acute lung injury>, HPLC of Formula: 6823-69-4, the main research area is acute lung injury exosome alveolar macrophage cell inflammation sepsis; Exosome; Inflammatory; MHs cells; Sepsis-induced acute lung injury.

Exosome is a novel tool with an essential role in cell communication. However, its role in the pathogenesis of sepsis-induced acute lung injury is currently unknown. Here, we first found that lipopolysaccharide (LPS) could up-regulate the expression of pro-inflammatory cytokines and promote exosomes release in the murine alveolar macrophage cell line (MHs cells). Moreover, we found MHs cells derived exosomes also maintain the pro-inflammatory effect after LPS stimulation. Treating with hydrochloride hydrate (GW4869) could dose-dependently downregulated the release of exosomes and inhibited the upregulation of inflammatory cytokines in MHs cells with LPS treatment. Also, we further identified GW4869 administration induced the remission of histopathol. changes, the reduction of pro-inflammatory cytokines in lung tissue, and inhibit serum exosomes release. These results indicate that the downregulation of exosome release by GW4869 might protect lung tissue from LPS induced injury through the suppression of excessive inflammatory responses, suggesting its potential therapeutic effects on sepsis-induced acute lung injury.

Respiratory Physiology & Neurobiology published new progress about Acute pulmonary injury. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, HPLC of Formula: 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Czernecki, Dariusz; Bonhomme, Frederic; Kaminski, Pierre-Alexandre; Delarue, Marc published the artcile< Characterization of a triad of genes in cyanophage S-2L sufficient to replace adenine by 2-aminoadenine in bacterial DNA>, Recommanded Product: 7H-Purin-2-amine, the main research area is .

Abstract: Cyanophage S-2L is known to profoundly alter the biophys. properties of its DNA by replacing all adenines (A) with 2-aminoadenines (Z), which still pair with thymines but with a triple hydrogen bond. It was recently demonstrated that a homolog of adenylosuccinate synthetase (PurZ) and a dATP triphosphohydrolase (DatZ) are two important pieces of the metabolism of 2-aminoadenine, participating in the synthesis of ZTGC-DNA. Here, we determine that S-2L PurZ can use either dATP or ATP as a source of energy, thereby also depleting the pool of nucleotides in dATP. Furthermore, we identify a conserved gene (mazZ) located between purZ and datZ genes in S-2L and related phage genomes. We show that it encodes a (d)GTP-specific diphosphohydrolase, thereby providing the substrate of PurZ in the 2-aminoadenine synthesis pathway. High-resolution crystal structures of S-2L PurZ and MazZ with their resp. substrates provide a rationale for their specificities. The Z-cluster made of these three genes – datZ, mazZ and purZ – was expressed in E. coli, resulting in a successful incorporation of 2-aminoadenine in the bacterial chromosomal and plasmidic DNA. This work opens the possibility to study synthetic organisms containing ZTGC-DNA.

Nature Communications published new progress about 452-06-2. 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

Manasieva, Leda Ivanova; Maria, Battisti Umberto; Prandi, Adolfo; Brasili, Livio; Franchini, Silvia published the artcile< Synthesis of Heteroaryl ortho-Phenoxyethylamines via Suzuki Cross-Coupling: Easy Access to New Potential Scaffolds in Medicinal Chemistry>, Recommanded Product: 5-Bromo-1-methyl-1H-imidazole, the main research area is heteroaryl ortho phenoxyethylamine preparation Suzuki cross coupling.

Heteroaryl ortho-phenoxyethylamines have been extensively employed in medicinal chem. as privileged scaffolds for the design of highly potent and selective ligands. Herein an efficient, fast, and general method for the synthesis of heteroaryl phenoxyethylamines via Suzuki cross-coupling is reported. This approach offers the opportunity to obtain a large variety of biaryls incorporating five-membered (thiophene, furan, thiazole, pyrazole, imidazole) or six-membered (pyridine, pyrimidine) heteroaromatic rings for appropriate libraries of ligands. All the compounds presented here have never been synthesized before and a full structural characterization is given.

Synthesis published new progress about Amines Role: SPN (Synthetic Preparation), PREP (Preparation) (phenoxyethylamines). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Recommanded Product: 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wang, Li-juan; Ren, Ming; Wang, Hou-xiu; Qiu, Jian-Ge; Jiang, BingHua; Zhang, Chun-yang published the artcile< Construction of a quencher-free cascade amplification system for highly specific and sensitive detection of serum circulating miRNAs>, Computed Properties of 452-06-2, the main research area is microRNA sequence strand displacement amplification blood human neoplasm diagnosis.

Circulating miRNAs are a newly emerging class of noninvasive biomarkers, and the accurate quantification of their expression is essential to the biol. research and early clinic diagnosis. Herein, we demonstrate the construction of a quencher-free cascade amplification system for highly sensitive detection of serum circulating miRNAs. The target miRNA can hybridize with the linear probe to induce the cyclic strand displacement amplification (SDA) (cycle I) for the production of the binding probes. The binding probe can subsequently react with the 2-aminopurine (2-AP)-hairpin probe to induce the recycling exonuclease cleavage of 2-AP-hairpin probes (cycle II), releasing the triggers and 2-AP mols. simultaneously. The released trigger can hybridize with the free linear probe to start new cycles I and II amplifications. Through multiple rounds of cascade amplifications, a large number of 2-AP mols. are released, generating an enhanced fluorescence signal. This method exhibits a large dynamic range of 8 orders of magnitude and a detection limit of 0.16 aM. It can differentiate a single-base mismatch in miR-486-5p, quantify miR-486-5p in lung cancer cells at various stages, and even discriminate the expressions of serum circulating miR-486-5p in healthy persons from that in nonsmall-cell lung carcinoma (NSCLC) patients. Moreover, this assay can be rapidly carried out in one step under isothermal condition in a label-free manner, holding promising applications in point-of-care diagnosis and prognosis of lung cancers.

Analytical Chemistry (Washington, DC, United States) published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (ARHGAP5). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Computed Properties of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Li, Quan; Li, Hanhao; Liang, Jinlian; Mei, Jiaxin; Cao, Zhen; Zhang, Lei; Luo, Jiao; Tang, Yan; Huang, Rufei; Xia, Huan; Zhang, Qihao; Xiang, Qi; Yang, Yan; Huang, Yadong published the artcile< Sertoli cell-derived exosomal MicroRNA-486-5p regulates differentiation of spermatogonial stem cell through PTEN in mice>, Reference of 6823-69-4, the main research area is sertoli cell exosomal miR4865p differentiation PTEN spermatogonial stem; Sertoli cells; differentiation; exosome; miR-486-5p; spermatogonial stem cells.

Self-renewal and differentiation of spermatogonial stem cell (SSC) are critical for male fertility and reproduction, both of which are highly regulated by testicular microenvironment. Exosomal miRNAs have emerged as new components in intercellular communication. However, their roles in the differentiation of SSC remain unclear. Here, we observed miR-486-5p enriched in Sertoli cell and Sertoli cell-derived exosomes. The exosomes mediate the transfer of miR-486-5p from Sertoli cells to SSCs. Exosomes release miR-486-5p, thus up-regulate expression of Stra8 (stimulated by retinoic acid 8) and promote differentiation of SSC. And PTEN was identified as a target of miR-486-5p. Overexpression of miR-486-5p in SSCs down-regulates PTEN expression, which up-regulates the expression of STRA8 and SYCP3, promotes SSCs differentiation. In addition, blocking the exosome-mediated transfer of miR-486-5p inhibits differentiation of SSC. Our findings demonstrate that miR-486-5p acts as a communication mol. between Sertoli cells and SSCs in modulating differentiation of SSCs. This provides a new insight on mol. mechanisms that regulates SSC differentiation and a basis for the diagnosis, treatment, and prevention of male infertility.

Journal of Cellular and Molecular Medicine published new progress about CD81 antigens 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