10 results on '"Kamzeeva, Polina N."'
Search Results
2. 8-Oxoadenine: A «New» Player of the Oxidative Stress in Mammals?
- Author
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Kruchinin, Alexander A., Kamzeeva, Polina N., Zharkov, Dmitry O., Aralov, Andrey V., and Makarova, Alena V.
- Subjects
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DNA ligases , *OXIDATIVE stress , *EUKARYOTIC cells , *DNA polymerases , *CELL physiology , *BACTERIAL cells , *GENETIC toxicology - Abstract
Numerous studies have shown that oxidative modifications of guanine (7,8-dihydro-8-oxoguanine, 8-oxoG) can affect cellular functions. 7,8-Dihydro-8-oxoadenine (8-oxoA) is another abundant paradigmatic ambiguous nucleobase but findings reported on the mutagenicity of 8-oxoA in bacterial and eukaryotic cells are incomplete and contradictory. Although several genotoxic studies have demonstrated the mutagenic potential of 8-oxoA in eukaryotic cells, very little biochemical and bioinformatics data about the mechanism of 8-oxoA-induced mutagenesis are available. In this review, we discuss dual coding properties of 8-oxoA, summarize historical and recent genotoxicity and biochemical studies, and address the main protective cellular mechanisms of response to 8-oxoA. We also discuss the available structural data for 8-oxoA bypass by different DNA polymerases as well as the mechanisms of 8-oxoA recognition by DNA repair enzymes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
3. Red light-emitting short Mango-based system enables tracking a mycobacterial small noncoding RNA in infected macrophages.
- Author
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Bychenko, Oksana S, Khrulev, Alexei A, Svetlova, Julia I, Tsvetkov, Vladimir B, Kamzeeva, Polina N, Skvortsova, Yulia V, Tupertsev, Boris S, Ivanov, Igor A, Aseev, Leonid V, Khodarovich, Yuriy M, Belyaev, Evgeny S, Kozlovskaya, Liubov I, Zatsepin, Timofei S, Azhikina, Tatyana L, Varizhuk, Anna M, and Aralov, Andrey V
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- 2023
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4. Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses.
- Author
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Rubekina, Anna A., Kamzeeva, Polina N., Alferova, Vera A., Shustova, Elena Yu., Kolpakova, Ekaterina S., Yakovchuk, Elizaveta V., Karpova, Evgenia V., Borodulina, Maria O., Belyaev, Evgeny S., Khrulev, Alexei A., Korshun, Vladimir A., Shirshin, Evgeny A., Kozlovskaya, Liubov I., and Aralov, Andrey V.
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ROSE bengal , *VIRUS inactivation , *XANTHENE dyes , *PHOTODYNAMIC therapy , *PHOTOSENSITIZATION , *SARS-CoV-2 - Abstract
Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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5. Cationic Perylene Antivirals with Aqueous Solubility for Studies In Vivo.
- Author
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Shtro, Anna A., Garshinina, Anzhelika V., Alferova, Vera A., Kamzeeva, Polina N., Volok, Viktor P., Kolpakova, Ekaterina S., Nikitin, Timofei D., Chistov, Alexey A., Belyaev, Evgeny S., Korshun, Vladimir A., Kozlovskaya, Liubov I., and Aralov, Andrey V.
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PERYLENE ,SOLUBILITY ,ANTIVIRAL agents ,CHEMICAL synthesis ,DRUG design ,LABORATORY mice - Abstract
Perylene-based compounds are attracting significant attention due to their high broad-spectrum antiviral activity against enveloped viruses. Despite unambiguous results of in vitro studies and high selectivity index, the poor water solubility of these compounds prevented in vivo evaluation of their antiviral properties. In this work, we synthesized a series of compounds with a perylene pharmacophore bearing positively charged substituents to improve the aqueous solubility of this unique type of antivirals. Three types of charged groups were introduced: (1) quaternary morpholinium salts (3a–b); (2) a 2′-O-l-valinyl-uridine hydrochloride residue (8), and (3) a 3-methylbenzothiazolium cation (10). The synthesized compounds were evaluated based both on antiviral properties in vitro (CHIKV, SARS-CoV-2, and IAV) and on solubility in aqueous media. Compound 10 has the greatest aqueous solubility, making it preferable for pre-evaluation by intragastrical administration in a mouse model of lethal influenza pneumonia. The results indicate that the introduction of a positively charged group is a viable strategy for the design of drug candidates with a perylene scaffold for in vivo studies. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Benzothiazole-substituted 1,3-diaza-2-oxophenoxazine as a luminescent nucleobase surrogate for silver(I)-mediated base pairing.
- Author
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Nyenhuis, Marvin, Schönrath, Isabell, Kamzeeva, Polina N., Zatsepin, Timofei S., Müller, Jens, Doltsinis, Nikos, and Aralov, Andrey V.
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BASE pairs ,TIME-dependent density functional theory ,DUPLEX ultrasonography - Abstract
A benzothiazole-substituted derivative (X) of 1,3-diaza-2-oxophenoxazine was evaluated with respect to its ability to engage in Ag(I)-mediated homo base pair formation in two different DNA duplexes. The metal binding was determined by a combination of temperature-dependent UV spectroscopy, CD spectroscopy, and fluorescence spectroscopy, indicating the incorporation of two Ag(I) ions to generate a dinuclear X–Ag(I)
2 –X base pair. Interestingly, a luminescence increase was observed upon metal binding. Theoretical luminescence spectra were calculated using time-dependent density functional theory (TDDFT) for all possible Ag(I)-mediated X : X base pair geometries to identify the species responsible for the increase in luminescence. The study shows that even bulky non-planar artificial nucleobases can be applied to form stabilizing metal-mediated base pairs. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
7. Probing GFP Chromophore Analogs as Anti-HIV Agents Targeting LTR-III G-Quadruplex.
- Author
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Ryazantsev, Dmitriy Y., Myshkin, Mikhail Yu., Alferova, Vera A., Tsvetkov, Vladimir B., Shustova, Elena Y., Kamzeeva, Polina N., Kovalets, Polina V., Zaitseva, Elvira R., Baleeva, Nadezhda S., Zatsepin, Timofei S., Shenkarev, Zakhar O., Baranov, Mikhail S., Kozlovskaya, Liubov I., and Aralov, Andrey V.
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ANTI-HIV agents ,GREEN fluorescent protein ,HIGH throughput screening (Drug development) ,TARGETED drug delivery ,MOLECULAR spectroscopy ,VIRAL genes ,FLUORESCENCE resonance energy transfer - Abstract
Green fluorescent protein (GFP) chromophore and its congeners draw significant attention mostly for bioimaging purposes. In this work we probed these compounds as antiviral agents. We have chosen LTR-III DNA G4, the major G-quadruplex (G4) present in the long terminal repeat (LTR) promoter region of the human immunodeficiency virus-1 (HIV-1), as the target for primary screening and designing antiviral drug candidates. The stabilization of this G4 was previously shown to suppress viral gene expression and replication. FRET-based high-throughput screening (HTS) of 449 GFP chromophore-like compounds revealed a number of hits, sharing some general structural features. Structure-activity relationships (SAR) for the most effective stabilizers allowed us to establish structural fragments, important for G4 binding. Synthetic compounds, developed on the basis of SAR analysis, exhibited high LTR-III G4 stabilization level. NMR spectroscopy and molecular modeling revealed the possible formation of LTR-III G4-ligand complex with one of the lead selective derivative ZS260.1 positioned within the cavity, thus supporting the LTR-III G4 attractiveness for drug targeting. Selected compounds showed moderate activity against HIV-I (EC50 1.78–7.7 μM) in vitro, but the activity was accompanied by pronounced cytotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
8. Anticancer activity of G4-targeting phenoxazine derivatives in vitro.
- Author
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Lizunova, Sofia A., Tsvetkov, Vladimir B., Skvortsov, Dmitry A., Kamzeeva, Polina N., Ivanova, Olga M., Vasilyeva, Lilja A., Chistov, Alexey A., Belyaev, Evgeny S., Khrulev, Alexei A., Vedekhina, Tatiana S., Bogomazova, Alexandra N., Lagarkova, Maria A., Varizhuk, Anna M., and Aralov, Andrey V.
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ANTINEOPLASTIC agents , *CELL nuclei , *NUCLEOSIDE derivatives , *LIVER cells , *PROMOTERS (Genetics) , *POISONS , *CANCER cells - Abstract
G4-stabilizing ligands are now being considered as anticancer, antiviral and antibacterial agents. Phenoxazine is a promising scaffold for the development of G4 ligands. Here, we profiled two known phenoxazine-based nucleoside analogs and five new nucleoside and non-nucleoside derivatives against G4 targets from telomere repeats and the KIT promoter region. Leading new derivatives exhibited remarkably high G4-stabilizing effects (comparable or superior to the effects of the commonly used selective G4 ligands PDS and NMM) and selectivity toward G4s over duplex (superior to BRACO-19). All phenoxazine-based ligands inhibited cellular metabolic activity. The phenoxazine derivatives were particularly toxic for lung adenocarcinoma cells A549' and human liver cancer cells HepG2 (CC 50 of the nucleoside analogues in the nanomolar range), but also affected breast cancer cells MCF7, as well as immortalized fibroblasts VA13 and embryonic kidney cells HEK293t (CC 50 in the micromolar range). Importantly, the CC 50 values varied mostly in accordance with G4-binding affinities and G4-stabilizing effects, and the phenoxazine derivatives localized in the cell nuclei, which corroborates G4-mediated mechanisms of action. • Phenoxazine-based derivatives were probed as G4 ligands. • Some derivatives exhibited remarkably high G4-stabilizing effects and selectivity. • All phenoxazine-based ligands inhibited cellular metabolic activity. • The ligands were particularly toxic for lung adenocarcinoma cells. • Localization in the cell nuclei corroborated G4-mediated mechanisms of action. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
9. Recent Advances in Molecular Mechanisms of Nucleoside Antivirals.
- Author
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Kamzeeva PN, Aralov AV, Alferova VA, and Korshun VA
- Abstract
The search for new drugs has been greatly accelerated by the emergence of new viruses and drug-resistant strains of known pathogens. Nucleoside analogues (NAs) are a prospective class of antivirals due to known safety profiles, which are important for rapid repurposing in the fight against emerging pathogens. Recent improvements in research methods have revealed new unexpected details in the mechanisms of action of NAs that can pave the way for new approaches for the further development of effective drugs. This review accounts advanced techniques in viral polymerase targeting, new viral and host enzyme targeting approaches, and prodrug-based strategies for the development of antiviral NAs.
- Published
- 2023
- Full Text
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10. Benzothiazole-substituted 1,3-diaza-2-oxophenoxazine as a luminescent nucleobase surrogate for silver(I)-mediated base pairing.
- Author
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Nyenhuis M, Schönrath I, Kamzeeva PN, Zatsepin TS, Müller J, Doltsinis N, and Aralov AV
- Subjects
- Base Pairing, Benzothiazoles, Oxazines, Luminescence, Silver chemistry
- Abstract
A benzothiazole-substituted derivative (X) of 1,3-diaza-2-oxophenoxazine was evaluated with respect to its ability to engage in Ag(I)-mediated homo base pair formation in two different DNA duplexes. The metal binding was determined by a combination of temperature-dependent UV spectroscopy, CD spectroscopy, and fluorescence spectroscopy, indicating the incorporation of two Ag(I) ions to generate a dinuclear X-Ag(I)
2 -X base pair. Interestingly, a luminescence increase was observed upon metal binding. Theoretical luminescence spectra were calculated using time-dependent density functional theory (TDDFT) for all possible Ag(I)-mediated X : X base pair geometries to identify the species responsible for the increase in luminescence. The study shows that even bulky non-planar artificial nucleobases can be applied to form stabilizing metal-mediated base pairs.- Published
- 2022
- Full Text
- View/download PDF
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