Month: October 2022

On July 1, 2019, Yang, Jianhong; Du, Jiatian; Huang, Chong; Wang, Tianqi; Huang, Luyi; Yang, Shengyong; Li, Linli published an article.COA of Formula: C5H4Br2N2O The title of the article was Discovery of 5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazin-2(1H)-one derivatives as new potent PB2 inhibitors. And the article contained the following:

PB2 is an important subunit of influenza RNA-dependent RNA polymerase (RdRP) and has been recognized as a promising target for the treatment of influenza. We herein report the discovery of a new series of PB2 inhibitors containing the skeleton 5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazin-2(1H)-one. Compound I is the most potent one, which showed KD values of 0.11 μM and 0.19 μM in surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) assays, resp. In antiviral activity and cellular cytotoxicity assays, compound I showed an EC50 value of 1.025 μM and a CC50 value greater than 100 μM. Mol. docking was also used to predict the binding mode of I with PB2. Collectively, this study provides a promising lead compound for subsequent anti-influenza drug discovery targeting PB2. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).COA of Formula: C5H4Br2N2O

The Article related to fluoropyrrolopyridinyl pyrazinone preparation pb2 inhibitor antiinfluenza antiviral activity, influenza a virus, pb2, small molecule inhibitor, structure-activity relationship and other aspects.COA of Formula: C5H4Br2N2O

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On December 1, 2019, Pinto da Silva, Luis; Nunez-Montenegro, Ara; Magalhaes, Carla M.; Ferreira, Paulo J. O.; Duarte, Diana; Gonzalez-Berdullas, Patricia; Rodriguez-Borges, Jose E.; Vale, Nuno; Esteves da Silva, Joaquim C. G. published an article.HPLC of Formula: 55779-48-1 The title of the article was Single-molecule chemiluminescent photosensitizer for a self-activating and tumor-selective photodynamic therapy of cancer. And the article contained the following:

While photodynamic therapy is known for significant advantages over conventional cancer therapies, its dependence on light has limited it to treating tumors on or just under the skin or on the outer lining of organs/cavities. Herein, we have developed a single-mol. photosensitizer capable of intracellular self-activation and with potential tumor-selectivity due to a chemiluminescent reaction involving only a cancer marker. Thus, the photosensitizer is directly chemiexcited to a triplet excited state capable of generating singlet oxygen, without requiring either a light source or any catalyst/co-factor. Cytotoxicity assays involving the photosensitizer show significant toxicity toward tumor cells, even better than reference drugs, while not inducing toxicity toward normal cells. This work provides a proof-of-concept for a novel type of photosensitizer that eliminates the current restrictions that photodynamic therapy presents regarding tumor size and localization. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).HPLC of Formula: 55779-48-1

The Article related to chemiluminescent photosensitizer cancer pdt photodynamic therapy, breast cancer, cancer, chemiluminescence, coelenterazine, photodynamic therapy, photosensitizer, prostate cancer and other aspects.HPLC of Formula: 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Bakayan, Adil; Picaud, Sandrine; Malikova, Natalia P.; Tricoire, Ludovic; Lambolez, Bertrand; Vysotski, Eugene S.; Peyrieras, Nadine published an article in 2020, the title of the article was RedquorinXS mutants with enhanced calcium sensitivity and bioluminescence output efficiently report cellular and neuronal network activities.Synthetic Route of 55779-48-1 And the article contains the following content:

Considerable efforts have been focused on shifting the wavelength of aequorin Ca2+-dependent blue bioluminescence through fusion with fluorescent proteins. This approach has notably yielded the widely used GFP-aequorin (GA) Ca2+ sensor emitting green light, and tdTomato-aequorin (Redquorin), whose bioluminescence is completely shifted to red, but whose Ca2+ sensitivity is low. In the present study, the screening of aequorin mutants generated at twenty-four amino acid positions in and around EF-hand Ca2+-binding domains resulted in the isolation of six aequorin single or double mutants (AequorinXS) in EF2, EF3, and C-terminal tail, which exhibited markedly higher Ca2+ sensitivity than wild-type aequorin in vitro. The corresponding Redquorin mutants all showed higher Ca2+ sensitivity than wild-type Redquorin, and four of them (RedquorinXS) matched the Ca2+ sensitivity of GA in vitro. RedquorinXS mutants exhibited unaltered thermostability and peak emission wavelengths. Upon stable expression in mammalian cell line, all RedquorinXS mutants reported the activation of the P2Y2 receptor by ATP with higher sensitivity and assay robustness than wt-Redquorin, and one, RedquorinXS-Q159T, outperformed GA. Finally, wide-field bioluminescence imaging in mouse neocortical slices showed that RedquorinXS-Q159T and GA similarly reported neuronal network activities elicited by the removal of extracellular Mg2+. Our results indicate that RedquorinXS-Q159T is a red light-emitting Ca2+ sensor suitable for the monitoring of intracellular signaling in a variety of applications in cells and tissues, and is a promising candidate for the transcranial monitoring of brain activities in living mice. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Synthetic Route of 55779-48-1

The Article related to redquorinxs mutant calcium sensitivity bioluminescence cellular neuronal network, bret, gpcr assay, aequorin, bioluminescence, calcium sensor, mutagenesis, neuronal network imaging and other aspects.Synthetic Route of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Nguyen, Hieu T. H.; Bouteau, Francois; Mazars, Christian; Kuse, Masaki; Kawano, Tomonori published an article in 2019, the title of the article was Enhanced elevations of hypo-osmotic shock-induced cytosolic and nucleic calcium concentrations in tobacco cells by pretreatment with dimethyl sulfoxide.Category: pyrazines And the article contains the following content:

DMSO (DMSO) is a dipolar aprotic solvent widely used in biol. assays. Here, we observed that DMSO enhanced the hypo-osmotically induced increases in the concentration of Ca2+ in cytosolic and nucleic compartments in the transgenic cell-lines of tobacco (BY-2) expressing aequorin. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Category: pyrazines

The Article related to calcium dimethyl sulfoxide aequorin nicotiana cell suspension cytosol nucleus, cytosolic calcium concentration, dimethyl sulfoxide, hypo-osmotic shock, nucleic calcium concentration and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 1, 2022, Aguinaga Martinez, Maite V.; Jozicova, Natali; Dusek, Jan; Horstkotte, Burkhard; Pavek, Petr; Miro, Manuel; Sklenarova, Hana published an article.Synthetic Route of 55779-48-1 The title of the article was Real-time monitoring of Metridia luciferase release from cells upon interaction with model toxic substances by a fully automatic flow setup – A proof of concept. And the article contained the following:

This manuscript reports on a fully automatic sequential injection system incorporating a 3D printed module for real-time monitoring of the release of Metridia luciferase from a modified liver epithelial cell line. To this end, a simple and effective approach for the automation of flash-type chemiluminescence assays was developed. The 3D printed module comprised an apical and a basal compartment that enabled monitoring membrane processes on both sides of the cell monolayer aimed at elucidating the direction of luciferase release. A natural release was observed after transfection with the luciferase plasmid by online measurement of the elicited light from the reaction of the synthesized luciferase with the coelenterazine substrate. Model substances for acute toxicity from the group of cholic acids – chenodeoxycholic and deoxycholic acids – were applied at the 1.0 and 0.5 mmol L-1 levels. The tested cholic acids caused changes in cell membrane permeability that was accompanied by an increased luciferase release. The obtained kinetic profiles were evaluated based on the delay between the addition of the toxic substance and the increase of the chemiluminescence signal. All experiments were carried out in a fully automatic system in ca. 5 min per sample in 30 min intervals and no manual interventions were needed for a sampling period of at least 6 h. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Synthetic Route of 55779-48-1

The Article related to metridia luciferase liver epithelial cell toxicity chemiluminescence, 3d-printing, automation, cell toxicity, metridia luciferase, real-time monitoring, sequential injection analysis and other aspects.Synthetic Route of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Nishihara, Ryo; Suzuki, Koji; Kim, Sung-Bae; Paulmurugan, Ramasamy published an article in 2021, the title of the article was Highly Bright NIR-BRET System for Imaging Molecular Events in Live Cells.COA of Formula: C26H21N3O3 And the article contains the following content:

The present protocol demonstrates a novel mammalian cell imaging platform exerting a bioluminescence resonance energy transfer (BRET) system. This platform achieves a ∼300 nm blue-to-near IR shift of the emission (NIR-BRET) with the development of a unique coelenterazine (CTZ) derivative named BBlue2.3 and a fusion reporter protein probe named iRFP-RLuc8.6-535SG. The best NIR-BRET shift was achieved by tuning the blue emission peak of BBlue2.3 to a Soret band of the iRFP. In mammalian cells, BBlue2.3 emits light that is ∼50-fold brighter than DeepBlueC in cell imaging when combined with RLuc8.6-535SG. This NIR-BRET platform is sufficiently brighter to be used for imaging live mammalian cells at single-cell level, and also for imaging metastases in deep tissues in live mice without generating considerable autoluminescence. This unique optical platform provides the brightest NIR-BLI template that can be used for imaging a diverse group of cellular events in living subjects. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).COA of Formula: C26H21N3O3

The Article related to live cells imaging mol events nir bret, bioluminescence imaging (bli), bioluminescence resonance energy transfer (bret), blue-to-near infrared shift, coelenterazine derivatives, metastasis and other aspects.COA of Formula: C26H21N3O3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Magalhaes, Carla M.; Gonzalez-Berdullas, Patricia; Duarte, Diana; Correia, Ana Salome; Rodriguez-Borges, Jose E.; Vale, Nuno; Esteves da Silva, Joaquim C. G.; Pinto da Silva, Luis published an article in 2021, the title of the article was Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect.Computed Properties of 55779-48-1 And the article contains the following content:

Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-mol. widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these mols. to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Computed Properties of 55779-48-1

The Article related to coelenterazine anticancer synthesis heavy atom, cancer, chemiluminescence, coelenterazine, heavy-atom effect, photodynamic therapy, self-activating photosensitizers, triplet chemiexcitation and other aspects.Computed Properties of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On June 7, 2019, Chaloupkova, Radka; Liskova, Veronika; Toul, Martin; Markova, Klara; Sebestova, Eva; Hernychova, Lenka; Marek, Martin; Pinto, Gaspar P.; Pluskal, Daniel; Waterman, Jitka; Prokop, Zbynek; Damborsky, Jiri published an article.Category: pyrazines The title of the article was Light-emitting dehalogenases: Reconstruction of multifunctional biocatalysts. And the article contained the following:

To obtain structural insights into the emergence of biol. functions from catalytically promiscuous enzymes, we reconstructed an ancestor of catalytically distinct, but evolutionarily related, haloalkane dehalogenases (EC 3.8.1.5) and Renilla luciferase (EC 1.13.12.5). This ancestor has both hydrolase and monooxygenase activities. Its crystal structure solved to 1.39 Å resolution revealed the presence of a catalytic pentad conserved in both dehalogenase and luciferase descendants and a mol. oxygen bound in between two residues typically stabilizing a halogen anion. The differences in the conformational dynamics of the specificity-determining cap domains between the ancestral and descendant enzymes were accessed by mol. dynamics and hydrogen-deuterium exchange mass spectrometry. Stopped-flow anal. revealed that the alkyl enzyme intermediate formed in the luciferase-catalyzed reaction is trapped by blockage of a hydrolytic reaction step. A single-point mutation (Ala54Pro) adjacent to one of the catalytic residues bestowed hydrolase activity on the modern luciferase by enabling cleavage of this intermediate. Thus, a single substitution next to the catalytic pentad may enable the emergence of promiscuous activity at the enzyme class level, and ancestral reconstruction has a clear potential for obtaining multifunctional catalysts. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Category: pyrazines

The Article related to light emitting dehalogenase hydrolase monooxygenase crystal structure conformation substrate, haloalkane dehalogenase luciferase ancestor hydrolase monooxygenase crystal structure conformation and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Nishihara, Ryo; Hoshino, Emi; Kakudate, Yoshiki; Suzuki, Koji; Kim, Sung-Bae published an article in 2021, the title of the article was Azide- and Dye-Conjugated Coelenterazine Analogues for Imaging Mammalian Cells.Recommanded Product: 55779-48-1 And the article contains the following content:

Coelenterazine (CTZ) is a common substrate to most marine luciferases and photoproteins. The present protocol introduces mammalian cell imaging with nine novel dye- and azide-conjugated CTZ analogs, which were synthesized by conjugating a series of fluorescent dyes or an azide group to the C-2 or C-6 position of CTZ backbone. The investigation on the optical properties revealed that azide-conjugated CTZs emit greatly selective bioluminescence (BL) to artificial luciferases (ALucs) and ca. 130 nm blue-shifted BL with Renilla luciferase variant 8.6 (RLuc8.6) in mammalian cells. The corresponding kinetic study explains that azide-conjugated CTZ exerts higher catalytic efficiency than CTZ. Nile red-conjugated CTZ completely showed red-shifted CRET spectra and characteristic BRET spectra with artificial luciferase 16 (ALuc16). The present protocol shows that the minimal spectral overlap occurs among the pairs of [Furimazine/NanoLuc], [6-N3-CTZ/ALuc26], [6-pi-OH-CTZ/RLuc8.6], and [6-N3-CTZ/RLuc8.6] because of the substrate-driven luciferase specificity or color shifts, convincing a cross talk-free multiplex bioassay platform. The present protocol introduces a new toolbox to bioassays and multiplex mol. imaging platforms for mammalian cells. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Recommanded Product: 55779-48-1

The Article related to artificial luciferase (aluc®), bioluminescence, bioluminescence resonance energy transfer (bret), chemiluminescence resonance energy transfer (cret), coelenterazine (ctz), renilla luciferase (rluc) and other aspects.Recommanded Product: 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Griffiths, Thomas M.; Oakley, Aaron J.; Yu, Haibo published an article in 2020, the title of the article was Atomistic insights into photoprotein formation: Computational prediction of the properties of coelenterazine and oxygen binding in obelin.COA of Formula: C26H21N3O3 And the article contains the following content:

Bioluminescence in marine systems is dominated by the use of coelenterazine for light production The bioluminescent reaction of coelenterazine is an enzyme catalyzed oxidative decarboxylation: coelenterazine reacts with mol. oxygen to form carbon dioxide, coelenteramide, and light. One such class is the Ca2+-regulated photoproteins. These proteins bind coelenterazine and oxygen, and trap 2-hydroperoxycoelenterazine, an intermediate along the reaction pathway. The reaction is halted until Ca2+ binding triggers the completion of the reaction. There are currently no reported exptl., atomistic descriptions of this ternary Michaelis complex. This study utilized computational techniques to develop an atomistic model of the Michaelis complex. Extensive mol. dynamics simulations were carried out to study the interactions between four tautomeric/protonation states of coelenterazine and wide-type and mutant obelin. Only minor differences in binding modes were observed across all systems. Interestingly, no basic residues were identified in the vicinity of the N7-nitrogen of coelenterazine. This observation was surprising considering that deprotonation at this position is a key mechanistic step in the proposed bioluminescent reaction. This work suggests that coelenterazine binds either as the O10H tautomer, or in the deprotonated form. Implicit ligand sampling simulations were used to identify potential O2 binding and migration pathways within obelin. A key oxygen binding site was identified close to the coelenterazine imidazopyrazinone core. The O2 binding free energy was observed to be dependent on the protonation state of coelenterazine. Taken together, the description of the obelin-coelenterazine-O2 complexes established in this study provides the basis for future computational studies of the bioluminescent mechanism. © 2019 Wiley Periodicals, Inc. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).COA of Formula: C26H21N3O3

The Article related to bioluminescence obelin obelia mechanism mol dynamics simulation coelenterazine oxygen, bioluminescence, implicit ligand sampling, molecular dynamics simulations, oxygen binding, photoprotein formation and other aspects.COA of Formula: C26H21N3O3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem