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Perylenyltriazoles inhibit reproduction of enveloped viruses
European Journal of Medicinal Chemistry. 2017. Vol. 138. P. 293-299.
Vladimir A. Korshun
1-Substituted 4-perylen-2(3)-y1-1,2,3-triazoles, easily accessible by 'click' reaction and combining in one molecule a polyaromatic unit and a nitrogen heterocycle, were found to strongly inhibit the reproduction of enveloped viruses. 5[4-(Perylen-3-y1)-1,2,3-triazol-1-y1]-uridine and 2-[1-(2-hydroxyethyl)-1,2,3triazol-4-yl]perylene show EC50 of 0.031 and 0.023 mu M, respectively, against tick-borne encephalitis virus (TBEV). Remarkably, the nucleoside unit appears to be not essential for antiviral activity. These results provide deeper understanding of structural basis of activity for this new class of antivirals.
Language:
English
Vladimir A. Korshun, European Journal of Medicinal Chemistry 2018 Vol. 155 P. 77-83
series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C1e4-alkyl-1,2,3-triazol-1,4-diyl groups at 30-O-position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds (4, 6, 8a, 8b) showed EC50 10 nM, thus appearing the most potent TBEV inhibitors ...
Added: November 8, 2019
Vladimir A. Korshun, European Journal of Medicinal Chemistry 2019 Vol. 171 P. 93-103
Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a
nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its
amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to
have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with
remarkable activity against ...
Added: November 8, 2019
Vladimir A. Korshun, Antiviral Research 2018 Vol. 149 P. 164-173
Most antivirals target viral proteins and are specific for only one virus, or viral type. Whereas viral proteins are encoded in the plastic viral genome, virion lipids are not and their rearrangements during fusion are conserved
among otherwise unrelated enveloped viruses. Antivirals that inhibit these lipid rearrangements could thus pose
a high barrier to resistance and have broad-spectrum ...
Added: November 8, 2019
Vladimir A. Korshun, Antiviral Research 2019 Vol. 163 P. 117-124
The phenoxazine scaffold is widely used to stabilize nucleic acid duplexes, as a part of fluorescent probes for the study of nucleic acid structure, recognition, and metabolism, etc. Here we present the synthesis of phenoxazine-based nucleoside derivatives and their antiviral activity against a panel of structurally diverse viruses: enveloped DNA herpesviruses varicella zoster virus (VZV) and human ...
Added: November 8, 2019
М. : Издательство "Перо", 2019
Сборник научных трудов включает материалы актовых и пленарных лекций, симпозиальных докладов, выступлений на заседаниях круглых столов и стендовых докладов, представленных на VI Съезде физиологов СНГ, VI Съезде биохимиков России и IX Российском симпозиуме «Белки и пептиды», которые прошли в рамках II Объединенного научного форума в Сочи–Дагомысе, 1–6 октября 2019 года. Тематика представленных докладов охватывает актуальные ...
Added: November 2, 2019
Vladimir A. Korshun, Prokhorenko I., Golovin A., Tetrahedron 2017 Vol. 73 No. 23 P. 3220-3230
1-Phenylethynylpyrene fluorophore (1-PEPy) has long-wavelength shifted emission and higher photostability
compared to pyrene, retaining, however, pyrene's ability to form excimers. Here we report the
synthesis of 2'-O-[3(and 4)-(pyren-1-ylethynyl)benzyl]-uridines and their tandem incorporation into
deoxyribo- and 2'-O-Me-ribo-oligonucleotide probes. Excimer forming probes of type NN … NNXXNN …
NN (X = 2'-O-[meta(or para)-(pyren-1-ylethynyl)-benzyl]uridine) containing two adjacent fluorescent
nucleosides within an oligonucleotide are ...
Added: November 6, 2019
М. : Энциклопедия, Инфра-М, 2017
The New Russian Encyclopedia is a fundamental reference publication in 18 volumes that characterizes nature, population, economy, history, science, art, technology and other important aspects. Contains about 60,000 articles, about 30,000 biographies, about 15,000 color illustrations, maps, charts, diagrams, tables. Leaves since 2003. ...
Added: October 29, 2018
Slesarchuk N., Khvatov E., Chistov A. et al., Bioorganic and Medicinal Chemistry Letters 2020 Vol. 30 No. 10 Article 127100
Rigid amphipathic fusion inhibitors are potent broad-spectrum antivirals based on the perylene scaffold, usually decorated with a hydrophylic group linked via ethynyl or triazole. We have sequentially simplified these structures by removing sugar moiety, then converting uridine to aniline, then moving to perylenylthiophenecarboxilic acids and to perylenylcarboxylic acid. All these polyaromatic compounds, as well as ...
Added: March 17, 2020
Gaisina I., Lee S., Kaidery N. et al., ACS Chemical Neuroscience 2018 Vol. 9 No. 5 P. 894-900
Activation of HIF-1α and Nrf2 is a primary component of cellular response to oxidative stress, and activation of HIF-1α and Nrf2 provides neuroprotection in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's and Parkinson's diseases. Screening a library of CNS-targeted drugs using novel reporters for HIF-1α and Nrf2 elevation in neuronal cells revealed histone deacetylase ...
Added: April 15, 2020
Valueva A., Romanov R., Vorobyeva N. et al., ACS Omega 2020 Vol. 5 No. 12 P. 6641-6650
Pyrophosphate arthropathy is the mineralization defect in humanscaused by the deposition of microcrystals of calcium pyrophosphate dihydrate injoint tissues. As a potential therapeutic strategy for the treatment of pyrophosphatearthropathy, delivery of exogenous pyrophosphate-hydrolyzing enzymes, inorganicpyrophosphatases (PPases), to the synovial fluid has been suggested. Previously,we synthesized the conjugates of Escherichia coli PPase (Ec-PPase) with detonationsynthesis nanodiamonds ...
Added: June 21, 2021
М. : Энциклопедия, Инфра-М, 2017
The New Russian Encyclopedia is a fundamental reference publication in 18 volumes that characterizes nature, population, economy, history, science, art, technology and other important aspects. Contains about 60,000 articles, about 30,000 biographies, about 15,000 color illustrations, maps, charts, diagrams, tables. Leaves since 2003. ...
Added: October 29, 2018
М. : Издательство "Перо", 2019
Сборник научных трудов включает материалы актовых и пленарных лекций, симпозиальных докладов, выступлений на заседаниях круглых столов и стендовых докладов, представленных на VI Съезде физиологов СНГ, VI Съезде биохимиков России и IX Российском симпозиуме «Белки и пептиды», которые прошли в рамках II Объединенного научного форума в Сочи–Дагомысе, 1–6 октября 2019 года. Тематика представленных докладов охватывает актуальные ...
Added: November 2, 2019
Poloznikov A., Nikulin S., Zakhariants A. et al., Drug Metabolism Letters 2019 Vol. 13 No. 1 P. 45-52
BACKGROUND "Branched tail" oxyquinolines, and adaptaquin in particular, are potent HIF prolyl hydroxylase inhibitors showing promising results in in vivo hemorrhagic stroke models. The further improvement of the potency resulted in identification of a number of adaptaquin analogs. Early evaluation of toxicity and metabolism is desired right at the step of lead selection. OBJECTIVE The ...
Added: April 17, 2020
Springer, 2019
This unique work compiles the latest knowledge around veterinary nutraceuticals, commonly referred to as dietary supplements, from ingredients to final products in a single source. More than sixty chapters organized in seven sections collate all related aspects of nutraceutical research in animal health and disease, among them many novel topics: common nutraceutical ingredients (Section-I), prebiotics, ...
Added: June 25, 2019
Vladimir A. Korshun, RSC advances 2019 Vol. 9 No. 45 P. 26014-26023
The propargylamide of N3-Pom-protected 5-(perylen-3-ylethynyl)uracil acetic acid, a universal precursor, was used in a CuAAC click reaction for the synthesis of several derivatives, including three ramified molecules with high activities against tick-borne encephalitis virus (TBEV). Pentaerythritol-based polyazides were used for the assembly of molecules containing 2/4 antiviral 5-(perylen-3-ylethynyl) uracil scaffolds, the first examples of polyvalent perylene antivirals. Cluster compounds ...
Added: November 8, 2019
М. : Энциклопедия, Инфра-М, 2018
The New Russian Encyclopedia is a fundamental reference publication in 18 volumes that characterizes nature, population, economy, history, science, art, technology and other important aspects. Contains about 60,000 articles, about 30,000 biographies, about 15,000 color illustrations, maps, charts, diagrams, tables. Leaves since 2003. ...
Added: October 28, 2018
Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus
Vladimir A. Korshun, Journal of General Virology 2018 Vol. 99 No. 1 P. 148-156
Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl) uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no ...
Added: November 8, 2019
Poloznikov A., Nikulin S., Hushpulian D. et al., Antioxidants 2022 Vol. 11 No. 2 Article 220
To evaluate the differences in action of commercially available 2-oxoglutarate mimetics and “branched-tail” oxyquinoline inhibitors of hypoxia-inducible factor prolyl hydroxylase (HIF PHD), the inhibitors’ IC50 values in the activation of HIF1 ODD-luciferase reporter were selected for comparative transcriptomics. Structure–activity relationship and computer modeling for the oxyquinoline series of inhibitors led to the identification of novel ...
Added: February 3, 2023
Nicol R., Chapman S., Vertes P. et al., Journal of Neurophysiology (США) 2012 Vol. 107 No. 5 P. 1421-1430
How do human brain networks react to dynamic changes in the sensory environment? We measured rapid changes in brain network organization in response to brief, discrete, salient auditory stimuli. We estimated network topology and distance parameters in the immediate central response period, <1 s following auditory presentation of standard tones interspersed with occasional deviant tones ...
Added: October 23, 2014
Andreev-Andrievskiy A., Roman A. Zinovkin, Mashkin M. et al., Frontiers in Pharmacology (Швейцария) 2021 No. 12 Article 679511
Clinical data evidence its safety and efficiency for the treatment of flu and other viral infections via enhancement of interferon production. The gut-associated lymphoid tissue seems a likely site of kagocel action. The study was aimed to investigate the molecular mechanisms of its action using murine Peyer’s patches lymphocytes as a test system and the ...
Added: December 10, 2022
Landrette S. F., Madera D., He F. et al., Leukemia 2011 Vol. 25 No. 4 P. 655-662
Cytokine signaling pathways are frequent targets of oncogenic mutations in acute myeloid leukemia (AML), promoting proliferation and survival. We have previously shown that the transcription factor PLAGL2 promotes proliferation and cooperates with the leukemia fusion protein Cbfβ-SMMHC in AML development. Here, we show that PLAGL2 upregulates expression of the thrombopoietin receptor Mpl, using two consensus ...
Added: April 21, 2021
Shchekotikhin A. E., Glazunova V.A., Dezhenkova L. G. et al., Bioorganic and Medicinal Chemistry 2009 Vol. 17 No. 5 P. 1861-1869
We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53-/- cells. The cytotoxicity of some novel compounds ...
Added: July 14, 2015
Tonevitsky A., Maltseva D., Obesity Reviews 2019 Vol. 20 No. 1 P. 108-118
Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology. Here we propose tissue‐cooperative, homeostatic model of NAFLD. During early stages of NAFLD the intrahepatic production of miR‐122 falls, while the secretion of miRNA‐containing exosomes by adipose increases. Bloodstream carries exosome to the liver, where their miRNA cargo is released to regulate their intrahepatic ...
Added: April 14, 2020
Tonevitsky A., Baranova A., Maltseva D., Obesity Reviews 2018 P. 1-11
Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology. Here we propose tissue-cooperative, homeostatic model of NAFLD. During early stages of NAFLD the intrahepatic production of miR-122 falls, while the secretion of miRNA-containing exosomes by adipose increases. Bloodstream carries exosome to the liver, where their miRNA cargo is released to regulate their intrahepatic ...
Added: October 30, 2018