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1.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Volobueva A. S., Zarubaev V. V., Fedorchenko T. G., Lipunova G. N., Tungusov V. N., Chupakhin O. N.
Заглавие : Antiviral properties of verdazyls and leucoverdazyls and their activity against group b enteroviruses
Место публикации : Russian journal of infection and immunity. - 2023. - Vol. 13, № 1. - С. 107-118
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): enteroviruses--enteroviral infection--coxsackievirus
Аннотация: Enteroviruses are non-enveloped viruses of Enterovirus genus, Picornaviridae family, causing a variety of human diseases: from acute respiratory and intestinal infections to more severe pathologies including poliomyelitis, encephalitis, myocarditis, pancreatitis. Currently, no approved direct-acting antiviral drugs for treatment of enterovirus infections exists, whereas vaccination is available only for prevention of poliomyelitis and enterovirus 71 infection. Therefore, it is promising to conduct a search for inhibitors of enteroviruses life cycle in drug development to treat enterovirus infections. Here, antiviral properties of stable free radicals, verdazyls, and their precursors, leucoverdazyls, were investigated. It has been shown that leucoverdazyls vs verdazyls increased the survival of permissive cell culture infected with coxsackievirus. The activity range of the lead leucoverdazyl against RNA-containing and DNA-containing human viruses (in the viral yield reduction assay) and its proposed mechanism of action (time of addition assay) was studied. The lead compound suppressed reproduction of group B enteroviruses in vitro, with modest activity against influenza A virus and no activity against herpes virus type 1 and adenovirus type 5. The maximum decrease in viral titers was observed upon its addition to infected cells during early and middle stages of the virus life cycle. Thus, we concluded that the studied compound has a pronounced inhibitory activity against group B enteroviruses not belonging to the class of capsid binder inhibitors, without virucidal properties. Previously, we described antioxidant properties of leucoverdazyls. It is known that many viral infections are accompanied by production of reactive oxygen species and oxidative stress, and some compounds with antioxidant properties exhibit antiviral potential. Targeted chemical modifications of leucoverdazyls and further studies of leucoverdazyl mechanism of action as well as in vivo animal studies are needed. However, the results obtained may be useful for future development of new antiviral drugs to treat enteroviral infections.
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2.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Krinochkin A. P., Shtaitz Y. K., Rammohan A., Butorin I. I., Savchuk M. I., Khalymbadzha I. A., Kopchuk D. S., Slepukhin P. A., Melekhin V. V., Shcheglova A. V., Zyryanov G. V., Chupakhin O. N.
Заглавие : 1H-pyrazole-appended pyridines and their 1,2,4-triazine precursors: a rational synthesis and in silico and in vitro evaluation of anti-cancer activity
Место публикации : European Journal of Organic Chemistry. - 2022. - Vol. 2022, № 22. - С. e202200227
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Аннотация: An operationally facile and high yielding one-pot protocol has been developed for the preparation of pyridines appended with pyrazole via NH linker. This protocol includes SNipso/aza-Diels-Alder reactions in up to 54 % yields starting from 1,2,4-triazine precursors. All the synthesized compounds have been evaluated for their in silico activity against JAK1, SYK, and FAK1 kinases. The most promising compound was tested in vitro using A-172, Hs578T, and HepG2 cancer cell lines and exhibited considerable cytotoxicity with IC50 values 50 μM in A-172 and HepG2 cell lines. Anticancer in vitro activity correlates well with the predicted in silico data.
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3.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Khudina O. G., Ivanova A. E., Burgart Ya. V., Gerasimova N. A., Evstigneeva N. P., Saloutin V. I.
Заглавие : Synthesis of mycostatics based on 4-aryldiazenyl-3,5-dimethylpyrazoles
Место публикации : Russian chemical bulletin. - 2021. - Vol. 70, № 6. - С. 1124-1130
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): 3-arylhydrazinylidenepentane-2,4-dione--condensation--hydrazines--4-aryldiazenyl-3,5-dimethylpyrazoles
Аннотация: The condensation of 3-arylhydrazinylidenepentane-2,4-diones with hydrazine hydrate, 2-hydroxyethylhydrazine, benzylhydrazine hydrochloride, and 4-hydrazinylbenzenesulfonamide hydrochloride gave 4-aryldiazenyl-3,5-dimethylpyrazoles. An alternative route to the synthesis of N-substituted 4-aryldiazenylpyrazoles is based on the alkylation of NH-pyrazoles with haloalkanes. The synthesized compounds were tested for antimicrobial activity against eight pathogenic dermatophytes, yeast-like fungi of the Candida genus and the bacteria Neisseria gonorrhoeae. The structure—activity relationship analysis showed that 4-tolyldiazenylpyrazoles bearing H, AcO(CH2)4, or HO(CH2)4 substituents at the N(1) atom have the highest mycostatic activity against all the dermatophyte strains under study. However, 4-aryldiazenyl-3,5-dimethylpyrazoles proved to be quite cytotoxic against the McCoy B cell line.
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4.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Dutysheva E. A., Utepova I. A., Trestsova M. A., Anisimov A. S., Charushin V. N., Chupakhin O. N., Margulis B. A., Guzhova I. V., Lazarev V. F.
Заглавие : Dataset of NMR-spectra pyrrolyl- and indolylazines and evidence of their ability to induce heat shock genes expression in human neurons
Место публикации : Data in Brief. - 2021. - № 39. - С. 107562
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): pyrrolylazines--indolylazines--photocatalysis--nuclear magnetic resonance--green chemistry
Аннотация: These data are related to our previous paper “Synthesis and approbation of new neuroprotective chemicals of pyrrolyl-and indolylazine classes in a cell model of Alzheimer’s disease” (Dutysheva et al., 2021), in which we demonstrate neu-roprotective abilities of pyrrolyl- and indolylazines in a cell model of Alzheimer’s disease. Using a novel procedure of photocatalysis we have synthesized a group of new compounds. The current article presents nuclear magnetic resonance spectra including heteronuclear single quantum coherence spectra of chemicals synthesized by us. The effect of new compounds have on heat shock proteins genes expression in reprogrammed human neurons are presented. We also presented data that verify neuronal phenotype of reprogrammed cells.
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5.

Вид документа :
Шифр издания : Г/U 61
Автор(ы) : Khamidullina L. A., Puzyrev I. S., Slepukhin P. A., Pestov A. V., Tobysheva P. D., Burygin G. L., Dorovatovskii P. V., Zubavichus Y. V., Mitrofanova A. V., Khrustalev V. N., Tskhovrebov A. G., Timofeeva T. V., Solari E., Nenajdenko V. G.
Заглавие : Unsymmetrical trifluoromethyl methoxyphenyl β-diketones: effect of the position of methoxy group and coordination at Cu(II) on biological activity
Место публикации : Molecules. - 2021. - Vol. 26, № 21. - Ст.6466
ББК : Г
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): copper(ii)--diketonates--cytotoxic activity--antimicrobial activity
Аннотация: Copper(II) complexes with 1,1,1-trifluoro-4-(4-methoxyphenyl)butan-2,4-dione (HL1) were synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single crystal X-ray diffraction. The biological properties of HL1 and cis-[Cu(L1)2(DMSO)] (3) were examined against Gram-positive and Gram-negative bacteria and opportunistic unicellular fungi. The cytotoxicity was estimated towards the HeLa and Vero cell lines. Complex 3 demonstrated antibacterial activity towards S. aureus comparable to that of streptomycin, lower antifungal activity than the ligand HL1 and moderate cytotoxicity. The bioactivity was compared with the activity of compounds of similar structures. The effect of changing the position of the methoxy group at the aromatic ring in the ligand moiety of the complexes on their antimicrobial and cytotoxic activity was explored. We propose that complex 3 has lower bioavailability and reduced bioactivity than expected due to strong intermolecular contacts. In addition, molecular docking studies provided theoretical information on the interactions of tested compounds with ribonucleotide reductase subunit R2, as well as the chaperones Hsp70 and Hsp90, which are important biomolecular targets for antitumor and antimicrobial drug search and design. The obtained results revealed that the complexes displayed enhanced affinity over organic ligands. Taken together, the copper(II) complexes with the trifluoromethyl methoxyphenyl-substituted β-diketones could be considered as promising anticancer agents with antibacterial properties
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6.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Varaksin M. V., Smyshliaeva L. A., Rusinov V. L., Melekhin V. V., Charushin V. N., Chupakhin O. N., Makeev O. G., Baldanshirieva A. D., Gubina O. G.
Заглавие : Synthesis, characterization, and in vitro assessment of cytotoxicity for novel azaheterocyclic nido-carboranes – Candidates in agents for boron neutron capture therapy (BNCT) of cancer
Место публикации : Tetrahedron. - 2021. - Vol. 102. - С. 132525
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): azaheterocycles--bnct--cytotoxicity--carboranes
Аннотация: A series of novel water-soluble azaheterocyclic derivatives of nido-carborane bearing quinoxaline, 2H-imidazole or 1,2,4-triazine moieties were first synthesized in 82–91% yields. The structures of these boron-enriched compounds were confirmed by the data of NMR, IR spectroscopy, and mass spectrometry. To access the toxicity level for these organoboron compounds, the cytotoxicity indexes (IC50) were determined using by the MTT test on both human glioblastoma cell A-172 (IC50 = 150–243 μM) and human embryonic lung cells (IC50 = 424–944 μM) lines. The obtained preliminary results from in vitro analysis enable the synthesized water-soluble azaheterocyclic carboranes to be considered as challenging candidates in the design of agents for boron-neutron capture therapy (BNCT) of malignant tumors.
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7.

Вид документа : Статья из журнала
Шифр издания : Г/P 58
Автор(ы) : Eltyshev A. K., Agafonova I. A., Minin A. S., Pozdina V. A., Shevirin V. A., Slepukhin P. A., Belskaya N. P., Benassi E.
Заглавие : Photophysics, photochemistry and bioimaging application of 8-azapurine derivatives
Место публикации : Organic & biomolecular chemistry. - 2021. - Vol. 19, № 45. - С. 9880-9896
ББК : Г
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Аннотация: New 2-aryl-1,2,3-triazolopyrimidines were designed, synthesized, and characterized. Their optical properties were thoroughly studied in the solid phase, in solution and in a biological environment. Density Functional Theory (DFT) based calculations were performed, including the molecular geometry optimization for both the ground state and the first singlet excited state, the prediction of the UV-Vis absorption and fluorescence spectra, the determination of the molecular electrostatic properties and the solvent effect on the optical properties. The emission intensity was revealed to increase in time upon irradiation. Mass spectrometric research, quantum mechanical calculations, and analysis of literature data suggested a possible photo-transformation pathway through the homolytic cleavage of one of the C–Cl bonds upon irradiation with UV light. The structure of the active intermediate was identified by the series of mass spectrometry experiments and via synthesis of putative transformation products. The kinetic parameters measured in different solvents allowed estimating the rate of these photo-transformations. Biological experiments demonstrated that 2-aryl-1,2,3-triazolopyrimidines penetrate cells and selectively accumulate in the cell membrane and the Golgi complex and endoplasmic reticulum. Their unique properties pave the way for new possible applications of fluorescent 8-azapurines in biology and medicine.
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8.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Bratskaya S., Skatova A., Privar Y., Boroda A., Kantemirova E., Maiorova M., Pestov A.
Заглавие : Stimuli-responsive dual cross-linked N-carboxyethylchitosan hydrogels with tunable dissolution rate
Место публикации : Gels. - 2021. - Vol. 7, № 4. - Ст.188
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): hydrogels--chitosan--salicylaldehyde
Аннотация: Here, we discuss the applicability of (methylenebis(salicylaldehyde)—MbSA) for the fabrication of the stimuli-responsive N-carboxyethylchitosan (CEC) hydrogels with a tunable dissolution rate under physiological conditions. In comparison with non-covalent salicylimine hydrogels, MbSA cross-linking via covalent bis(‘imine clip’) and non-covalent hydrophobic interactions allowed the fabrication of hydrogels with storage moduli 1 kPa at ten-fold lower aldehyde/CEC molar ratio with the preservation of pH- and amino-acid responsive behavior. Although MbSA-cross-linked CEC hydrogels were stable at neutral and weakly alkaline pH, their disassembly in cell growth medium (Dulbecco’s modified Eagle’s medium, DMEM) under physiological conditions was feasible due to transimination reaction with amino acids contained in DMEM. Depending on the cross-linking density, the complete dissolution time of the fabricated hydrogels varied from 28 h to 11 days. The cytotoxicity of MbSA cross-linked CEC hydrogels toward a human colon carcinoma cell line (HCT 116) and primary human dermal fibroblasts (HDF) was remarkably lower in comparison with CEC-salicylimine hydrogels. Fast gelation, relatively low cytotoxicity, and tunable stimuli-induced disassembly under physiological conditions make MbSA cross-linked CEC hydrogels promising for drug encapsulation and release, 3D printing, cell culturing, and other biomedical applications.
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9.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Demin A. M., Kandarakov O. F., Minin A. S., Kuznetsov D. K., Uimin M. A., Shur V. Ya., Belyavsky A. V., Krasnov V. P.
Заглавие : Modification of chemically and physically obtained Fe3O4 magnetic nanoparticles with L-Lys for cell labeling
Место публикации : Russian chemical bulletin. - 2021. - Vol. 70, № 6. - С. 1199-1208
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Аннотация: Peculiar features of the modification of Fe3O4 magnetic nanoparticles (MNPs) obtained by co-precipitation from solutions of FeII and FeIII salts (10-nm MNPs) and by the gas-condensation method (30-nm MNPs) with 3-aminopropylsilane and then with L-lysine were studied. The chemically obtained MNPs possess more pronounced hydrophilic properties and therefore readily form stable aqueous colloidal solutions and can be loaded with a larger amount of L-Lys. However, samples based on the physically obtained MNPs were characterized by more efficient internalization and longer retention times by the NIH 3T3 cells. The results obtained can be used in the design of novel nanomaterials for magnetic cell labeling.
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10.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Rammohan A., Zyryanov G. V.
Заглавие : Minireview: Remdesivir, a prominent nucleotide/nucleoside antiviral drug
Место публикации : Polycyclic aromatic compounds. - 2021. - Vol. 42, № 8. - С. 5824-5831
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Ключевые слова (''Своб.индексиров.''): antiviral drug--nucleotide analogue--remdesivir
Аннотация: Nucleotide analogues are the divergent scaffolds that are reliable potential therapeutic drugs to treat the wide range of diseases including viral infections. For instance, Remdesivir is a biologically important nucleotide analogue prodrug that can act as a key drug target for the diseases Ebola and COVID-19. Remdesivir is a structurally chiral aryloxy-phosphoramidate prodrug as it is metabolized into nucleoside triphosphate (active drug form) inside the cell through sequential reactions by ester mediated-hydrolysis. Thus, the current minireview focuses on the earlier reported synthetic approaches of key fragments of remdesivir and their developments to attain the scale-up yields of the drug for clinical/commercial applies. Further, this review serves as a template for the design and development of other complex organic molecules.
https://doi.org/10.1080/10406638.2021.1947331
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