- A Double-Clicking Bis-Azide Fluorogenic Dye for Bioorthogonal Self-Labeling Peptide Tags
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Herein, we give the very first example for the development of a fluorogenic molecular probe that combines the two-point binding specificity of biarsenical-based dyes with the robustness of bioorthogonal click-chemistry. This proof-of-principle study reports on the synthesis and fluorogenic characterization of a new, double-quenched, bis-azide fluorogenic probe suitable for bioorthogonal two-point tagging of small peptide tags by double strain-promoted azide-alkyne cycloaddition. The presented probe exhibits remarkable increase in fluorescence intensity when reacted with bis-cyclooctynylated peptide sequences, which could also serve as possible self-labeling small peptide tag motifs. The first example of a fluorogenic molecular probe has been developed that combines the two-point binding specificity of biarsenical-based dyes with the robustness of bioorthogonal click-chemistry. The new, double-quenched, bis-azide fluorogenic probe can bind to small bis-cyclooctynylated peptide tags through a double strain-promoted click reaction (see figure; SPAAC=strain-promoted alkyne-azide cycloaddition). The probe exhibits remarkable increase in fluorescence intensity with peptide sequences that can serve as possible self-labeling small peptide tags.
- Demeter, Orsolya,Fodor, Eszter A.,Kállay, Mihály,Mez, Gábor,Németh, Krisztina,Szabó, Pál T.,Kele, Péter
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Read Online
- Efficient synthesis of a new bifunctional Cu(I) chelator
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Abstract Herein we report an efficient eight-step synthesis of N1-(3-(methylthio)propyl)-2-((3-(methylthio)propyl)thio)benzene-1,4-diamine (1) from 6-nitrobenzo[d]thiazole. Incorporation of a nitro rather than a hydroxyl functionality off the a
- Massing, Justin O.,Planalp, Roy P.
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Read Online
- Design, synthesis and biological evaluation of new benzoxazolone/benzothiazolone derivatives as multi-target agents against Alzheimer's disease
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In this study, four series of compounds with benzoxazolone and benzothiazolone cores were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease (AD). Additionally, in order to shed light on the effect of the carbonyl groups of benzoxazolone/benzothiazolone, benzoxazole/benzothiazole-containing analogues were also synthesized and evaluated. Inhibition potency of all final compounds towards cholinesterase enzymes and their antioxidant activity were tested. Subsequently, the anti-inflammatory activity, cytotoxicity, apoptosis, and Aβ aggregation inhibition tests were also performed for selected compounds. The results indicated that compounds 11c, a pentanamide derivative with benzothiazolone core, and 14b, a keton derivative with benzothiazolone core, were considered as promising multi-functional agents for further investigation against AD. The reversibility, kinetic and molecular docking studies were also performed for the compounds with the highest AChE 14b (eeAChE IC50 = 0.34 μM, huAChE IC50 = 0.46 μM) and BChE 11c (eqBChE IC50 = 2.98 μM, huBChE IC50 = 2.56 μM) inhibitory activities.
- Erdogan, Merve,Kilic, Burcu,Sagkan, Rahsan Il?kc?,Aksakal, Fatma,Ercetin, Tugba,Gulcan, Hayrettin O.,Dogruer, Deniz S.
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- Green synthesis and biological evaluation of 6-substituted-2-(2-hydroxy/methoxy phenyl)benzothiazole derivatives as potential antioxidant, antibacterial and antitumor agents
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We present a new efficient green synthetic protocol for introduction of substituents to the C-6 position of 2-arylbenzothiazole nuclei. Newly synthesized compounds were designed to study the influence of the hydroxy and methoxy groups on the 2-arylbenzothiazole scaffold, as well as the influence of the type of substituents placed on the C-6 position of benzothiazole moiety on biological activity, including antibacterial, antitumor and antioxidant activity. Modest activity was observed against the tested Gram-positive and Gram-negative bacterial strains for only amidino derivatives 5d and 6d. The tested compounds exhibited moderate to strong antiproliferative activity towards the tumor cell lines tested. The SAR study revealed that the introduction of substituents into the benzene ring of the benzothiazole nuclei is essential for antiproliferative activity, while introduction of the hydroxy group into the 2-aryl moiety of the 2-arybenzothiazole scaffold significantly improved selectivity against tumor cell lines. The observed results revealed several novel 6-substituted-2-arylbenzothiazole compounds, 5b, 5c, 5f and 6f, with strong and selective antiproliferative activity towards HeLa cells in micro and submicromolar concentrations, with the most selective compounds being 6-ammonium-2-(2-hydroxy/methoxyphenyl)benzothiazoles 5f and 6f. The compound 5f bearing the hydroxy group on the 2-arylbenzothiazole core showed the most promising antioxidative activity evaluated by DPPH, ABTS and FRAP in vitro assays. The presence of the amino protonated group attached at the benzothiazole moiety was essential for the antiproliferative and antioxidant activity observed, exerted through a change in the levels of the reactive oxygen species-modulated HIF-1 protein.
- Racané, Livio,Pti?ek, Lucija,Fajdeti?, Glorija,Trali?-Kulenovi?, Vesna,Klobu?ar, Marko,Kraljevi? Paveli?, Sandra,Peri?, Mihaela,Paljetak, Hana ?ip?i?,Verbanac, Donatella,Star?evi?, Kristina
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- Rapid and scalable assembly of firefly luciferase substrates
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Bioluminescence imaging with luciferase-luciferin pairs is a popular method for visualizing biological processes in vivo. Unfortunately, most luciferins are difficult to access and remain prohibitively expensive for some imaging applications. Here we report cost-effective and efficient syntheses of d-luciferin and 6′-aminoluciferin, two widely used bioluminescent substrates. Our approach employs inexpensive anilines and Appel's salt to generate the luciferin cores in a single pot. Additionally, the syntheses are scalable and can provide multi-gram quantities of both substrates. The streamlined production and improved accessibility of luciferin reagents will bolster in vivo imaging efforts. This journal is
- McCutcheon, David C.,Porterfield, William B.,Prescher, Jennifer A.
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supporting information
p. 2117 - 2121
(2015/03/18)
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- A COMPOUND AND PHARMACEUTICAL COMPOUND FOR TREATMENT OF INFLAMMATORY DISEASES
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The present invention relates to a pharmaceutical composition for treating inflammatory diseases, comprising: a compound represented by chemical formula I, a pharmaceutically acceptable salt thereof; a hydrate thereof; or a compound as a solvate thereof,
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Paragraph 0146-0148
(2016/10/07)
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- SELECTIVE ANDROGEN RECEPTOR MODULATORS
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This invention provides compounds of formula I, pharmaceutical compositions comprising a compound of formula I and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds and intermediates useful in the preparation of same.
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Page/Page column 43
(2012/04/23)
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- Fluorescence properties of 5-(5,6-dimethoxybenzothiazol-2-yl)-2′- deoxyuridine (dbtU) and oligodeoxyribonucleotides containing d btU
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We describe the synthesis and photophysical properties of 11 substituted 5-(benzothiazol-2-yl)-2′-deoxyuridine derivatives and oligodeoxyribonucleotides (ODNs) containing 5-(5,6-dimethoxybenzothiazol-2-yl)- 2′-deoxyuridine (dbtU), which was the strongest fluorescent derivative among those prepared. The fluorescence properties of dbtU itself and ODNs containing dbtU show the same tendency of being weaker in both neutral and acidic solution and stronger in basic solution. The ODNs (15mer) containing 16 combinations of 5′-XbtU-3′ and 5′-btUY-3′, where X, Y = A, T, G, or C, were synthesized, and their fluorescence intensity and quantum yield in basic solution were compared. On average, only the ODN with the 5′-G btU-3′ sequence shows a 7.9-fold lower fluorescence intensity than the other sequences. Ab initio calculations of 5′-G btU-3′ and 5′-btUG-3′ as models under basic conditions suggest that the lower fluorescence of the ODN containing the 5′-GbtU-3′ sequence is caused by a wider overlap between stacked guanine (Gua) and btUra than that of the 5′- btUG-3′ sequence and that the HOMO is delocalized not only on btUra but also on Gua.
- Hirose, Wataru,Sato, Kousuke,Matsuda, Akira
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p. 6206 - 6217
(2011/12/02)
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- BENZOXAZINES, BENZOTHIAZINES, AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
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The present invention features benzoxazines, benzothiazines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inh
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Page/Page column 43-44
(2010/02/17)
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- Novel amidino substituted 2-phenylbenzothiazoles: Synthesis, antitumor evaluation in vitro and acute toxicity testing in vivo
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The efficient synthesis of new bis-substituted nitro-amidino, amino-amidino (10a, 10b-13a, 13b) and previously prepared diamidino 2-phenyl-benzothiazoles (9a, 9b) is described. The compounds 11a and 11b were prepared by recently developed methodology of the key precursors in zwitterionic form 8a and 8b with 4-nitrobenzoylchloride in a very good yield (70%). All compounds except diamidino-substituted 2-phenylbenzothiazole 9a show exceptionally prominent tumor cell-growth inhibitory activity and cytotoxicity, whereby the special selectivity of amino-amidine 2-phenylbenzothiazole 12a towards MCF-7 and H 460 cells makes this compound a prospective lead compound that should be further evaluated in animal models. All in vivo tested compounds (12a, 12b, 13a and 13b) are absorbed from mice gastrointestinal system. LD50 are between 67.33 and 696.2 mg/kg body weight (OECD/EPA toxicity categories 2-3).
- Racané, Livio,Kralj, Marijeta,?uman, Lidija,Stojkovi?, Ranko,Trali?-Kulenovi?, Vesna,Karminski-Zamola, Grace
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body text
p. 1038 - 1044
(2010/04/26)
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- 5,6-DIHYDRO-1H-PYRIDIN-2-ONE COMPOUNDS
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The invention is directed to 5,6-dihydro-1H-pyridin-2-one compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.
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Page/Page column 139-140
(2008/12/06)
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- PYRIDAZINONE COMPOUNDS
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The invention is directed to pyridazinone compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.
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Page/Page column 29
(2010/11/30)
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- PYRRO[1,2-B]PYRIDAZINONE COMPOUNDS
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The invention is directed to pyrro[l,2-b]pyridazinone compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.
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Page/Page column 58; 85
(2008/06/13)
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- HETEROCYCLIC ANTIVIRAL COMPOUNDS
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Compounds having the formula Ia or Ib wherein R1, R2, R3 and R4 are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection a
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Page/Page column 16; 26
(2008/06/13)
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- Heterocyclic antiviral compounds
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Compounds having the formula I wherein A, m and R1 are herein defined are Hepatitis C virus polymerase inhibitors. Also disclosed are compositions and methods for treating diseases mediated by HCV and for inhibiting hepatitis replication. Also disclosed are processes for making the compounds and synthetic intermediates used in the process
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Page/Page column 27
(2008/06/13)
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- N-aryl-2-oxazolidinone-5-carboxamides and their derivatives
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The present invention provides antibacterial agents having the formulae I, II, and III described herein.
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- N-ARYL-2-OXAZOLIDINONE-5-CARBOXAMIDES AND THEIR DERIVATIVES AND THEIR USE AS ANTIBACTERIALS
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Compounds of formula B-C-A-CO-NH-R1, wherein A is structure i, ii or iii: formulae (I), (II), (III). C is optionally substituted aryl or heteroaryl, and B is a specified cyclic moiety, or C and B together are a heterobicyclic moiety, are useful as antibacterial agents.
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Page/Page column 142
(2010/02/07)
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