Author: Jessica.F

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

On November 10, 2011, Barbosa, Antonio J. M.; Blomgren, Peter A.; Currie, Kevin S.; Krishnamoorthy, Ravi; Kropf, Jeffrey E.; Lee, Seung H.; Mitchell, Scott A.; Ortwine, Daniel; Schmitt, Aaron C.; Wang, Xiaojing; Xu, Jianjun; Young, Wendy; Zhang, Honglu; Zhao, Zhongdong; Zhichkin, Pavel E. published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Preparation of pyridone and azapyridone compounds as Btk inhibitors for treating immune disorders, inflammation, cancer, and other Btk-mediated diseases. And the patent contained the following:

The invention is related to the preparation of pyridones and azapyridones I [R1 = H, D, F, CN, OH, etc.; R2-4 = independently alkyl, Cl, NH2, OEt, etc.; R5 = (un)substituted (hetero)aryl, carbocyclyl, etc.; X = (S)0-2, N, NR6, O, CH and derivatives; R6 = H, F, NH2, OH, (un)substituted alkyl; Y, Y’ = independently CR6, N; Z1-4 = independently C, CH and derivatives, N; Z5 = CO, CH2 and derivatives, CH:N and derivatives, NH and derivatives, etc.; one of Z1 and Z2 or X and Z1, where X is not (S)0-2, forms a 5-7 membered aryl, carbocyclyl, heterocyclyl, heteroaryl ring; where alkyl, aryl, carbocyclyl, heterocyclyl, heteroaryl are optionally substituted] their stereoisomers, tautomers, and pharmaceutically acceptable salts useful for inhibiting Btk kinase, and for treating immune disorders, inflammation, cancer, and other Btk-mediated diseases. Methods of using I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathol. conditions, are disclosed. Thus, a multi-step synthesis starting from 5-nitropyrazole-3-carboxylic acid via cyclization of 1-(2-Bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole to 5-Methyl-2-nitro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine and cyclization of Et 1-(2-Aminoethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate to 3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one was given for II. II inhibited Btk kinase (IC50 = 0.002 μM). The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

The Article related to pyridone azapyridone preparation btk inhibitor immune disease inflamation cancer, benzothienopyridinone pyrazinoindolone pyrazinobenzimidazolone methanopyrazinoindolone preparation rheumatoid arthritis and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 28, 2015, Laurent, Alain; Rose, Yannick published a patent.Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone The title of the patent was Preparation of 8-aminoimidazo[3,4-a]pyrazine as Btk protein kinase inhibitors. And the patent contained the following:

The present invention relates to a novel family of protein kinase inhibitors, more specifically the present invention is directed to inhibitors of the members of the Tec and Src protein kinase families. The present invention also relates to processes for the preparation of these compounds [I; X = CH or N; R = H or each (un)substituted alkyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; W = OCH2R11 or CH2OR11; R1 = each (un)substituted aryl or heteroaryl; X1, X2 = H or halogen; m, m1 = an integer from O to 4] or pharmaceutically acceptable salts, solvates, solvates of salts, stereoisomers, tautomers, isotopes, prodrugs, complexes or biol. active metabolites thereof, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative, inflammatory, inflammatory and autoimmune diseases, disorders or conditions in which protein kinase activity is implicated. Thus, a solution of intermediate (II) (300 mg), intermediate (III) (397 mg), N,N-dimethylglycine (231 mg), cesium carbonate (1.1 g) and copper(I) iodide (141 mg) in 1,4-dioxane (1.5 mL) was heated in a pressure vessel at 110° overnight and then cooled to room temperature, followed by adding Et acetate, adsorbing the resulting mixture on silica gel, and purification by silica gel chromatog. to give 8-amino-1-(4-phenoxyphenyl)imidazo[3,4-a]pyrazine derivative (IV) as yellow solid. The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

The Article related to aminoimidazopyrazine aminophenoxyphenylimidazopyrazine preparation btk protein kinase inhibitor, proliferative disease inflammatory disease inflammatory autoimmune disease treatment aminoimidazopyrazine and other aspects.Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On March 15, 2015, Young, Wendy B.; Barbosa, James; Blomgren, Peter; Bremer, Meire C.; Crawford, James J.; Dambach, Donna; Gallion, Steve; Hymowitz, Sarah G.; Kropf, Jeffrey E.; Lee, Seung H.; Liu, Lichuan; Lubach, Joseph W.; Macaluso, Jen; Maciejewski, Pat; Maurer, Brigitte; Mitchell, Scott A.; Ortwine, Daniel F.; Di Paolo, Julie; Reif, Karin; Scheerens, Heleen; Schmitt, Aaron; Sowell, C. Gregory; Wang, Xiaojing; Wong, Harvey; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; Currie, Kevin S. published an article.Recommanded Product: 87486-34-8 The title of the article was Potent and selective Bruton’s tyrosine kinase inhibitors: Discovery of GDC-0834. And the article contained the following:

SAR studies focused on improving the pharmacokinetic (PK) properties of the previously reported potent and selective Btk inhibitor CGI-1746 resulted in the clin. candidate GDC-0834, which retained the potency and selectivity of CGI-1746, but with much improved PK in preclin. animal models. Structure based design efforts drove this work as modifications to CGI-1746 were investigated at both the solvent exposed region as well as ‘H3 binding pocket’. However, in vitro metabolic evaluation of GDC-0834 revealed a non CYP-mediated metabolic process that was more prevalent in human than preclin. species (mouse, rat, dog, cyno), leading to a high-level of uncertainly in predicting human pharmacokinetics. Due to its promising potency, selectivity, and preclin. efficacy, a single dose IND was filed and GDC-0834 was taken in to a single dose phase I trial in healthy volunteers to quickly evaluate the human pharmacokinetics. In human, GDC-0834 was found to be highly labile at the exo-cyclic amide bond that links the tetrahydrobenzothiophene moiety to the central aniline ring, resulting in insufficient parent drug exposure. This information informed the back-up program and discovery of improved inhibitors. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Recommanded Product: 87486-34-8

The Article related to bruton tyrosine kinase inhibitor gdc0834 preparation structure activity pharmacokinetics, amide hydrolysis, bruton’s tyrosine kinase, btk, gdc-0834, kinase inhibitor, rheumatoid arthritis, single dose ind and other aspects.Recommanded Product: 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Nishihara, Ryo; Paulmurugan, Ramasamy; Nakajima, Takahiro; Yamamoto, Eiji; Natarajan, Arutselvan; Afjei, Rayhaneh; Hiruta, Yuki; Iwasawa, Naoko; Nishiyama, Shigeru; Citterio, Daniel; Sato, Moritoshi; Kim, Sung Bae; Suzuki, Koji published an article in 2019, the title of the article was Highly bright and stable NIR-BRET with blue-shifted coelenterazine derivatives for deep-tissue imaging of molecular events in vivo.Category: pyrazines And the article contains the following content:

Bioluminescence imaging (BLI) is one of the most widely used optical platforms in mol. imaging, but it suffers from severe tissue attenuation and autoluminescence in vivo. Here, we developed a novel BLI platform on the basis of bioluminescence resonance energy transfer (BRET) for achieving a ∼300 nm blue-to-near IR shift of the emission (NIR-BRET) by synthesizing an array of 18 novel coelenterazine (CTZ) derivatives, named “Bottle Blue (BBlue)” and a unique iRFP-linked RLuc8.6-535SG fusion protein as a probe. The best NIR-BRET was achieved by tuning the emission peaks of the CTZ derivatives to a Soret band of the iRFP. In mammalian cells, BBlue2.3, one of the CTZ derivatives, emits light that is ∼50-fold brighter than DBlueC when combined with RLuc8.6-535SG, which shows stable BL kinetics. When we used a caged version of BBLue2.3, it showed a BL half decay time of over 60 min while maintaining the higher signal sensitivity. This NIR BL 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. A single-chain probe developed based on this BLI platform allowed us to sensitively image ligand antagonist-specific activation of estrogen receptor in the NIR region. 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 including protein-protein interactions and cancer metastasis. 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 nir bioluminescence resonance energy transfer coelenterazine, bioluminescence imaging, bioluminescence resonance energy transfer (bret), blue-to-near infrared shift, coelenterazine derivatives, metastasis and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Pinto da Silva, Luis; Magalhaes, Carla M.; Nunez-Montenegro, Ara; Ferreira, Paulo J. O.; Duarte, Diana; Rodriguez-Borges, Jose E.; Vale, Nuno; Esteves da Silva, Joaquim C. G. published an article in 2019, the title of the article was Study of the combination of self-activating photodynamic therapy and chemotherapy for cancer treatment.Category: pyrazines And the article contains the following content:

Cancer is a very challenging disease to treat, both in terms of treatment efficiency and side-effects. To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Anal. of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable. 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 breast neoplasm cell tamoxifen photodynamic therapy chemotherapy, anticancer drug, breast cancer, chemiluminescence, chemotherapy, multidrug combinations, photodynamic therapy, photosensitizer, prostate cancer and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Sousa, Joao; Magalhaes, Carla M.; Gonzalez-Berdullas, Patricia; Esteves da Silva, Joaquim C. G.; Pinto da Silva, Luis published an article in 2022, the title of the article was Comparative Investigation of the Chemiluminescent Properties of a Dibrominated Coelenterazine Analog.Recommanded Product: 55779-48-1 And the article contains the following content:

Chemi- and bioluminescence are remarkable light-emitting phenomena, in which thermal energy is converted into excitation energy due to a (bio)chem. reaction. Among a wide variety of chemi-/bioluminescent systems, one of the most well-known and studied systems is that of marine imidazopyrazinones, such as Coelenterazine and Cypridina luciferin. Due to the increasing usefulness of their chemi-/bioluminescent reactions in terms of imaging and sensing applications, among others, significant effort has been made over the years by researchers to develop new derivatives with enhanced properties. Herein, we report the synthesis and chemiluminescent characterization of a novel dibrominated Coelenterazine analog. This novel compound consistently showed superior luminescence, in terms of total light output and emission lifetime, to natural imidazopyrazinones and com. available analogs in aprotic media, while being capable of yellow light emission. Finally, this new compound showed enhanced chemiluminescence in an aqueous solution when triggered by superoxide anion, showing potential to be used as a basis for optimized probes for reactive oxygen species. In conclusion, bromination of the imidazopyrazinone scaffold appears to be a suitable strategy for obtaining Coelenterazines with enhanced properties. 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 dibrominated coelenterazine comparative investigation chemiluminescent property, cypridina luciferin, bioluminescence, chemiluminescence, coelenterazine, coelenterazine analogues, luminescence, superoxide anion and other aspects.Recommanded Product: 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem