Ramified derivatives of 5-(perylen-3-ylethynyl)uracil-1-acetic acid and their antiviral properties

Sapozhnikova, Ksenia A.; Slesarchuk, Nikita A.; Orlov, Alexey A.; Khvatov, Evgeny V.; Radchenko, Eugene V.; Chistov, Alexey A.; Ustinov, A. V.; Palyulin, Vladimir A.; Kozlovskaya, Liubov I.; Osolodkin, Dmitry I.; Korshun, Vladimir A.; Brylev, Vladimir A.

doi:10.1039/c9ra06313g

Cited by 9 publications

(7 citation statements)

References 72 publications

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“…This observation is in line with previous studies of perylene‐based antivirals, showing the best‐to‐date anti‐TBEV activity. [ 17,35–39 ]…”

Section: Resultsmentioning

confidence: 99%

“…This observation is in line with previous studies of perylene-based antivirals, showing the best-to-date anti-TBEV activity. [17,[35][36][37][38][39] Yellow fever virus appeared to be generally less susceptible to the studied compounds than TBEV or WNV. While the strains of the latter ones were initially isolated from natural sources, the YFV 17D strain is a live-attenuated vaccine strain, selected to be safe for human use.…”

Section: S C H E M Ementioning

confidence: 95%

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Tetrahydroquinazoline N‐oxide derivatives inhibit reproduction of tick‐borne and mosquito‐borne flaviviruses

Sedenkova

Uvarova

Назарова

et al. 2023

Archiv der Pharmazie

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Tick‐borne encephalitis virus (TBEV), yellow fever virus (YFV), and West Nile virus (WNV) are flaviviruses causing emerging arthropod‐borne infections of a great public health concern. Clinically approved drugs are not available to complement or replace the existing vaccines, which do not provide sufficient coverage. Thus, the discovery and characterization of new antiflaviviral chemotypes would advance studies in this field. In this study, a series of tetrahydroquinazoline N‐oxides was synthesized, and the antiviral activity of the compounds was assessed against TBEV, YFV, and WNV using the plaque reduction assay along with the cytotoxicity to the corresponding cell lines (porcine embryo kidney and Vero). Most of the studied compounds were active against TBEV (EC50 2 to 33 μM) and WNV (EC50 0.15 to 34 μM) and a few also demonstrated inhibitory activity against YFV (EC50 0.18 to 41 μM). To investigate the potential mechanism of action of the synthesized compounds, time‐of‐addition (TOA) experiments and virus yield reduction assays were performed for TBEV. The TOA studies suggested that the antiviral activity of the compounds should affect the early stages of the viral replication cycle after cell entry. Compounds with tetrahydroquinazoline N‐oxide scaffold show a broad spectrum of activity against flaviviruses and represent a promising chemotype for antiviral drug discovery.

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“…This observation is in line with previous studies of perylene‐based antivirals, showing the best‐to‐date anti‐TBEV activity. [ 17,35–39 ]…”

Section: Resultsmentioning

confidence: 99%

Section: S C H E M Ementioning

confidence: 95%

Tetrahydroquinazoline N‐oxide derivatives inhibit reproduction of tick‐borne and mosquito‐borne flaviviruses

Sedenkova

Uvarova

Назарова

et al. 2023

Archiv der Pharmazie

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“…Oligonucleotide synthesis, modification reagents, sequences, purification methods, protocols of click reactions of alkyne oligonucleotides with oligoethylene glycol and pentaerhytritol-derived diazides, , high-performance liquid chromatography (HPLC) traces, electrospray ionization mass spectrometry (ESI-MS) data, conditions for optimization of hybridization reactions, and atomic force microscopy experimental procedure − are described in the Supporting Information.…”

Section: Experimental Sectionmentioning

confidence: 99%

Toehold-Mediated Selective Assembly of Compact Discrete DNA Nanostructures

et al. 2020

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Production of small discrete DNA nanostructures containing covalent junctions requires reliable methods for the synthesis and assembly of branched oligodeoxynucleotide (ODN) conjugates. This study reports an approach for self-assembly of hard-to-obtain primitive discrete DNA nanostructures“nanoethylenes”, dimers formed by double-stranded oligonucleotides using V-shaped furcate blocks. We scaled up the synthesis of V-shaped oligonucleotide conjugates using pentaerythritol-based diazide and alkyne-modified oligonucleotides using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and optimized the conditions for “nanoethylene” formation. Next, we designed nanoethylene-based “nanomonomers” containing pendant adapters. They demonstrated smooth and high-yield spontaneous conversion into the smallest cyclic product, DNA tetragon aka “nano-methylcyclobutane”. Formation of DNA nanostructures was confirmed using native polyacrylamide gel electrophoresis (PAGE) and atomic force microscopy (AFM) and additionally studied by molecular modeling. The proposed facile approach to discrete DNA nanostructures using precise adapter-directed association expands the toolkit for the realm of DNA origami.

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“…These compounds inhibited the replication of HCMV [ 17 ], VZV [ 18 ], HIV [ 19 ] and HCV [ 20 ]. Moreover, ramified derivatives of uracil presented antiviral activity against tick-borne encephalitis virus (TBEV) [ 21 ]. In the present study, we evaluated the antiviral activity of novel uracil derivatives against SARS-CoV-2 in vitro to determine their potential for further study as novel antiviral compounds against SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Antiviral Activity of N1,N3-Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern

Siniavin

Новиков

Gushchin

et al. 2022

IJMS

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Despite the widespread use of the COVID-19 vaccines, the search for effective antiviral drugs for the treatment of patients infected with SARS-CoV-2 is still relevant. Genetic variability leads to the continued circulation of new variants of concern (VOC). There is a significant decrease in the effectiveness of antibody-based therapy, which raises concerns about the development of new antiviral drugs with a high spectrum of activity against VOCs. We synthesized new analogs of uracil derivatives where uracil was substituted at the N1 and N3 positions. Antiviral activity was studied in Vero E6 cells against VOC, including currently widely circulating SARS-CoV-2 Omicron. All synthesized compounds of the panel showed a wide antiviral effect. In addition, we determined that these compounds inhibit the activity of recombinant SARS-CoV-2 RdRp. Our study suggests that these non-nucleoside uracil-based analogs may be of future use as a treatment for patients infected with circulating SARS-CoV-2 variants.

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Ramified derivatives of 5-(perylen-3-ylethynyl)uracil-1-acetic acid and their antiviral properties

Abstract: Ramified clusters of antiviral perylenylethynyl scaffold were prepared using CuAAC reaction of 5-(perylen-3-ylethynyl)-3-pivaloyloxymethyl-1-(propargylamidomethyl)uracil with azides. Compounds inhibited TBEV reproduction at nanomolar concentrations.

Cited by 9 publications

References 72 publications

Tetrahydroquinazoline N‐oxide derivatives inhibit reproduction of tick‐borne and mosquito‐borne flaviviruses

Tetrahydroquinazoline N‐oxide derivatives inhibit reproduction of tick‐borne and mosquito‐borne flaviviruses

Toehold-Mediated Selective Assembly of Compact Discrete DNA Nanostructures

Antiviral Activity of N1,N3-Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern

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