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Authors = Tatiana A. Timofeeva

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15 pages, 3962 KiB  
Article
Changes in the Composition and Properties of Cultured Bacterial Strains of Ginseng Rhizosphere According to Soil Characteristics in the Forest and Plots
by Tatiana Y. Gorpenchenko, Marina L. Sidorenko, Alexandra V. Kim, Yuliya V. Vologzhanina, Darya A. Rusakova, Yana O. Timofeeva, Polina A. Perepelkina, Vitalii M. Kazarin and Yuriy N. Zhuravlev
Agronomy 2024, 14(12), 3019; https://doi.org/10.3390/agronomy14123019 - 18 Dec 2024
Viewed by 816
Abstract
The cultivation of Panax ginseng C.A. Meyer, a valuable medicinal plant, presents a number of challenges due to its physiology and life cycle. The composition of the soil and the microbiome living in it are important for plant growth and root quality. Modern [...] Read more.
The cultivation of Panax ginseng C.A. Meyer, a valuable medicinal plant, presents a number of challenges due to its physiology and life cycle. The composition of the soil and the microbiome living in it are important for plant growth and root quality. Modern analytical methods were used to identify differences in the rhizosphere soils of plants in the forest and in the plots. Microbiological and molecular genetic methods were used to isolate and identify bacterial isolates from these soils, allowing for the establishment of a working collection of potentially useful bacterial strains. Increases in soil pH in the plots and changes in the amount of macronutrients partially explained the changes in the activity of the forest and plot isolates and the composition of the cultivated strains. The cultivated strains belonged to the rhizosphere-dominant phyla Pseudomonadota, Bacillota, and Actinomycetota of the main functional groups of soil potassium, phosphorus, and nitrogen transformations. The ratio of bacteria functional groups was comparable in the forest and in the plots. The most common phylum of cultured microorganisms was Bacillota, while the main differences were observed in the functional group of potassium-solubilizing bacteria belonging to the phyla Pseudomonadota. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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18 pages, 3384 KiB  
Article
Phenylalanine Ammonia-Lyase-Mediated Differential Response of Tomato (Solanum lycopersicum L.) Cultivars with Different Stress Tolerance to Treatment with Low-Molecular-Weight Chitosan
by Tatiana A. Timofeeva, Anastasiya N. Bubnova, Balzhima T. Shagdarova, Valery P. Varlamov and Anastasiya M. Kamionskaya
Agronomy 2024, 14(2), 386; https://doi.org/10.3390/agronomy14020386 - 17 Feb 2024
Cited by 3 | Viewed by 2679
Abstract
The latest research has shown that chitosan acts as a growth stimulator and elicitor in plants, including resistance to biotic and abiotic factors. However, increasing concentrations could possibly make chitosan a source of stress for plants. In this study, we investigated the effect [...] Read more.
The latest research has shown that chitosan acts as a growth stimulator and elicitor in plants, including resistance to biotic and abiotic factors. However, increasing concentrations could possibly make chitosan a source of stress for plants. In this study, we investigated the effect of low-molecular-weight chitosan hydrolysate on the root development of tomato (Solanum lycoperscum) cultivars Red Cherry, Lel, and Tytan. The growth rate change, together with total phenolic content, phenylalanine ammonia-lyase (PAL) activity, and gene expression, were studied in relation to tomatoes. High concentrations of chitosan negatively affect the growth of tomato seedlings and contribute to changes in the tropism of the seedling roots. After the addition of chitosan hydrolysate, the PAL activity and the total phenolic content decreased 24 h later. PAL is a key enzyme in the biosynthesis of many plant stress factors. An analysis of the tomato PAL gene family was carried out. The SlPAL gene expression in the seedlings of cv. Cherry increased 1.5 times after 48 h, while in cv. Lel, the expression stably decreased in the presence of chitosan. The obtained results are supposed to aid our understanding of the mechanisms underlying the effects of chitosan on plant development and further its successful application in agriculture as well as in research on plant stress. Full article
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16 pages, 1096 KiB  
Article
Antigenic Architecture of the H7N2 Influenza Virus Hemagglutinin Belonging to the North American Lineage
by Aleksandr V. Lyashko, Tatiana A. Timofeeva, Irina A. Rudneva, Natalia F. Lomakina, Anastasia A. Treshchalina, Alexandra S. Gambaryan, Evgenii V. Sorokin, Tatiana R. Tsareva, Simone E. Adams, Alexey G. Prilipov, Galina K. Sadykova, Boris I. Timofeev, Denis Y. Logunov and Alexander L. Gintsburg
Int. J. Mol. Sci. 2024, 25(1), 212; https://doi.org/10.3390/ijms25010212 - 22 Dec 2023
Cited by 2 | Viewed by 1581
Abstract
The North American low pathogenic H7N2 avian influenza A viruses, which lack the 220-loop in the hemagglutinin (HA), possess dual receptor specificity for avian- and human-like receptors. The purpose of this work was to determine which amino acid substitutions in HA affect viral [...] Read more.
The North American low pathogenic H7N2 avian influenza A viruses, which lack the 220-loop in the hemagglutinin (HA), possess dual receptor specificity for avian- and human-like receptors. The purpose of this work was to determine which amino acid substitutions in HA affect viral antigenic and phenotypic properties that may be important for virus evolution. By obtaining escape mutants under the immune pressure of treatment with monoclonal antibodies, antigenically important amino acids were determined to be at positions 125, 135, 157, 160, 198, 200, and 275 (H3 numbering). These positions, except 125 and 275, surround the receptor binding site. The substitutions A135S and A135T led to the appearance of an N-glycosylation site at 133N, which reduced affinity for the avian-like receptor analog and weakened binding with tested monoclonal antibodies. Additionally, the A135S substitution is associated with the adaptation of avian viruses to mammals (cat, human, or mouse). The mutation A160V decreased virulence in mice and increased affinity for the human-type receptor analog. Conversely, substitution G198E, in combination with 157N or 160E, displayed reduced affinity for the human-type receptor analog. Full article
(This article belongs to the Special Issue Antiviral Drug Design, Synthesis and Molecular Mechanisms)
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17 pages, 1889 KiB  
Article
Hydrolysis–Dehydration of Cellulose: Efficiency of NbZr Catalysts under Batch and Flow Conditions
by Nikolay V. Gromov, Olga L. Ogorodnikova, Tatiana B. Medvedeva, Valentina N. Panchenko, Irina S. Yakovleva, Lyubov A. Isupova, Maria N. Timofeeva, Oxana P. Taran, Cyril Aymonier and Valentin N. Parmon
Catalysts 2023, 13(9), 1298; https://doi.org/10.3390/catal13091298 - 15 Sep 2023
Cited by 3 | Viewed by 1550
Abstract
Niobium oxide supported on ZrO2 and mixed oxide of NbOx-ZrO2 was prepared and characterized. Mechanical treatment was followed by the microwave heating procedure of catalysts with more advanced textural parameters. The amount of Lewis (LAS) and Brønsted (BAS) acid [...] Read more.
Niobium oxide supported on ZrO2 and mixed oxide of NbOx-ZrO2 was prepared and characterized. Mechanical treatment was followed by the microwave heating procedure of catalysts with more advanced textural parameters. The amount of Lewis (LAS) and Brønsted (BAS) acid sites rose with the increasing Nb content in the catalysts. The catalytic properties of samples of niobia-zirconia (NbZr samples, NbZr catalysts) were studied in a cellulose hydrolysis–dehydration reaction at 453 K under an inert Ar atmosphere in a batch reactor. Glucose and 5-hydroxumethylfurfural (5-HMF) were the major products. The initial reaction rate could be tuned by the density of acid sites on the surface of solid. At a low density of acid sites (0.1–0.3 µmol·m−2), the initial reaction rate had a pronounced inverse correlation. Increasing the LAS/BAS from 0.3 to 2.5 slightly stimulated the formation of the target products. The catalytic properties of NbZr catalysts prepared by microwave treatment were studied in cellulose transformation in a flow set-up. Glucose was found to be the major product. The maximum yield of glucose was observed in the presence of the sample of 17%Nb/ZrO2. Increasing Nb content resulted in the formation of Nb-associated acid centers and, in turn, increasing catalyst acidity and activity. Full article
(This article belongs to the Section Catalytic Materials)
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18 pages, 4414 KiB  
Article
Effects of Apatite Concentrate in Combination with Phosphate-Solubilizing Microorganisms on the Yield of Ryegrass Cultivar Izorskiy
by Tatiana A. Timofeeva, Vladimir K. Chebotar, Dmitriy V. Demidov, Sofia E. Gaidukova, Irina V. Yakovleva and Anastasia M. Kamionskaya
Agronomy 2023, 13(6), 1568; https://doi.org/10.3390/agronomy13061568 - 8 Jun 2023
Cited by 9 | Viewed by 2537
Abstract
Soil microorganisms play a vital role in increasing the availability of phosphorus (P) for plants through mineralization of organic P and solubilization of precipitated P compounds. In this two-year study, we analyzed several P-solubilizing microorganisms (PSMs) of the genus Bacillus and their consortiums [...] Read more.
Soil microorganisms play a vital role in increasing the availability of phosphorus (P) for plants through mineralization of organic P and solubilization of precipitated P compounds. In this two-year study, we analyzed several P-solubilizing microorganisms (PSMs) of the genus Bacillus and their consortiums for the ability to release soluble P from apatite concentrates of various grinding degrees using ryegrass (Lolium multiflorum Lam.) as a model plant. The effects were accessed by analyzing plant growth and nutrient assimilation. The greatest effect on root system development and plant biomass accumulation (dry weight) was observed for the apatite concentrate of standard grinding in combination with Bacillus megaterium BI14 and Bacillus subtilis BI2 and Bacillus velezensis BS89 strains. Although the introduction of apatite concentrates led to an increase in the content of total strontium in soil, the levels of strontium did not exceed the maximum allowable concentration, and the accumulation of mobile strontium by plants was unchanged; importantly, the use of tested PSMs led to a decrease in the strontium content in the green biomass of ryegrass. Our results indicate that biologized apatite concentrates in combination with PSMs represent promising fertilizers that can provide a source of soluble P to be readily assimilated by plants. Full article
(This article belongs to the Special Issue How Could Microorganisms Benefit the Agriculture Environment?)
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17 pages, 3446 KiB  
Article
Influenza A Virus M1 Protein Non-Specifically Deforms Charged Lipid Membranes and Specifically Interacts with the Raft Boundary
by Anna S. Loshkareva, Marina M. Popova, Liudmila A. Shilova, Natalia V. Fedorova, Tatiana A. Timofeeva, Timur R. Galimzyanov, Petr I. Kuzmin, Denis G. Knyazev and Oleg V. Batishchev
Membranes 2023, 13(1), 76; https://doi.org/10.3390/membranes13010076 - 7 Jan 2023
Cited by 9 | Viewed by 4172
Abstract
Topological rearrangements of biological membranes, such as fusion and fission, often require a sophisticated interplay between different proteins and cellular membranes. However, in the case of fusion proteins of enveloped viruses, even one molecule can execute membrane restructurings. Growing evidence indicates that matrix [...] Read more.
Topological rearrangements of biological membranes, such as fusion and fission, often require a sophisticated interplay between different proteins and cellular membranes. However, in the case of fusion proteins of enveloped viruses, even one molecule can execute membrane restructurings. Growing evidence indicates that matrix proteins of enveloped viruses can solely trigger the membrane bending required for another crucial step in virogenesis, the budding of progeny virions. For the case of the influenza A virus matrix protein M1, different studies report both in favor and against M1 being able to produce virus-like particles without other viral proteins. Here, we investigated the physicochemical mechanisms of M1 membrane activity on giant unilamellar vesicles of different lipid compositions using fluorescent confocal microscopy. We confirmed that M1 predominantly interacts electrostatically with the membrane, and its ability to deform the lipid bilayer is non-specific and typical for membrane-binding proteins and polypeptides. However, in the case of phase-separating membranes, M1 demonstrates a unique ability to induce macro-phase separation, probably due to the high affinity of M1’s amphipathic helices to the raft boundary. Thus, we suggest that M1 is tailored to deform charged membranes with a specific activity in the case of phase-separating membranes. Full article
(This article belongs to the Special Issue Membrane Regulation of Protein Function)
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19 pages, 3238 KiB  
Article
Natural IgG against S-Protein and RBD of SARS-CoV-2 Do Not Bind and Hydrolyze DNA and Are Not Autoimmune
by Anna M. Timofeeva, Sergey E. Sedykh, Evgeny A. Ermakov, Andrey L. Matveev, Eva I. Odegova, Tatiana A. Sedykh, Dmitry N. Shcherbakov, Iuliia A. Merkuleva, Ekaterina A. Volosnikova, Valentina S. Nesmeyanova, Nina V. Tikunova and Georgy A. Nevinsky
Int. J. Mol. Sci. 2022, 23(22), 13681; https://doi.org/10.3390/ijms232213681 - 8 Nov 2022
Cited by 10 | Viewed by 2576
Abstract
Since the onset of the COVID-19 pandemic, numerous publications have appeared describing autoimmune pathologies developing after a coronavirus infection, with several papers reporting autoantibody production during the acute period of the disease. Several viral diseases are known to trigger autoimmune processes, and the [...] Read more.
Since the onset of the COVID-19 pandemic, numerous publications have appeared describing autoimmune pathologies developing after a coronavirus infection, with several papers reporting autoantibody production during the acute period of the disease. Several viral diseases are known to trigger autoimmune processes, and the appearance of catalytic antibodies with DNase activity is one of the earliest markers of several autoimmune pathologies. Therefore, we analyzed whether IgG antibodies from blood plasma of SARS-CoV-2 patients after recovery could bind and hydrolyze DNA. We analyzed how vaccination of patients with adenovirus Sputnik V vaccine influences the production of abzymes with DNase activity. Four groups were selected for the analysis, each containing 25 patients according to their relative titers of antibodies to S-protein: with high and median titers, vaccinated with Sputnik V with high titers, and a control group of donors with negative titers. The relative titers of antibodies against DNA and the relative DNase activity of IgGs depended very much on the individual patient and the donor, and no significant correlation was found between the relative values of antibodies titers and their DNase activity. Our results indicate that COVID-19 disease and vaccination with adenoviral Sputnik V vaccine do not result in the development or enhancement of strong autoimmune reactions as in the typical autoimmune diseases associated with the production of anti-DNA and DNA hydrolyzing antibodies. Full article
(This article belongs to the Special Issue Autoimmunity and COVID-19)
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13 pages, 1623 KiB  
Article
Formic Acid Production via One-Pot Hydrolysis-Oxidation of Starch over Quaternary Ammonium Salts of Vanadium-Containing Keggin-Type Heteropoly Acids
by Nikolay V. Gromov, Tatiana B. Medvedeva, Ivan A. Lukoyanov, Valentina N. Panchenko, Maria N. Timofeeva, Oxana P. Taran and Valentin N. Parmon
Catalysts 2022, 12(10), 1252; https://doi.org/10.3390/catal12101252 - 17 Oct 2022
Cited by 11 | Viewed by 2727
Abstract
Bifunctional solid acidic quaternary ammonium salts of Keggin-type vanadium-containing heteropoly acids, such as R3.5H0.5PVMo11O40 (R: (C2H5)4N, (C4H9)4N, (C6H13)4N), [...] Read more.
Bifunctional solid acidic quaternary ammonium salts of Keggin-type vanadium-containing heteropoly acids, such as R3.5H0.5PVMo11O40 (R: (C2H5)4N, (C4H9)4N, (C6H13)4N), and [(C4H9)4N]4.5H0.5SiW11VO40, are capable of one-pot hydrolysis-oxidationconversion (OxFA-processing) of starch to biogenic formic acid. The impact of the reaction conditions and catalyst type was revealed. The highest formic acid yield of 50% was achieved over the best [(C2H5)4N]3.5H0.5PVMo11O40 catalyst, which was active and stable in seven reaction cycles. The kinetic computational model, which described formic acid formation well, was proposed in the presence of the most active [(C2H5)4N]3.5H0.5PVMo11O40 catalyst. Full article
(This article belongs to the Special Issue Mechanism/Kinetic Modeling Study of Catalytic Reactions)
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21 pages, 4028 KiB  
Article
Isolation and Characterization of a Novel Hydrophobin, Sa-HFB1, with Antifungal Activity from an Alkaliphilic Fungus, Sodiomyces alkalinus
by Anastasia E. Kuvarina, Eugene A. Rogozhin, Maxim A. Sykonnikov, Alla V. Timofeeva, Marina V. Serebryakova, Natalia V. Fedorova, Lyudmila Y. Kokaeva, Tatiana A. Efimenko, Marina L. Georgieva and Vera S. Sadykova
J. Fungi 2022, 8(7), 659; https://doi.org/10.3390/jof8070659 - 23 Jun 2022
Cited by 12 | Viewed by 2905
Abstract
The adaptations that alkaliphilic microorganisms have developed due to their extreme habitats promote the production of active natural compounds with the potential to control microorganisms, causing infections associated with healthcare. The primary purpose of this study was to isolate and identify a hydrophobin, [...] Read more.
The adaptations that alkaliphilic microorganisms have developed due to their extreme habitats promote the production of active natural compounds with the potential to control microorganisms, causing infections associated with healthcare. The primary purpose of this study was to isolate and identify a hydrophobin, Sa-HFB1, from an alkaliphilic fungus, Sodiomyces alkalinus. A potential antifungal effect against pathogenic and opportunistic fungi strains was determined. The MICs of Sa-HFB1 against opportunistic and clinical fungi ranged from 1 to 8 µg/mL and confirmed its higher activity against both non- and clinical isolates. The highest level of antifungal activity (MIC 1 µg/mL) was demonstrated for the clinical isolate Cryptococcus neoformans 297 m. The hydrophobin Sa-HFB1 may be partly responsible for the reported antifungal activity of S. alkalinus, and may serve as a potential source of lead compounds, meaning that it can be developed as an antifungal drug candidate. Full article
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16 pages, 1736 KiB  
Article
Exploring Peptaibol’s Profile, Antifungal, and Antitumor Activity of Emericellipsin A of Emericellopsis Species from Soda and Saline Soils
by Anastasia E. Kuvarina, Irina A. Gavryushina, Maxim A. Sykonnikov, Tatiana A. Efimenko, Natalia N. Markelova, Elena N. Bilanenko, Sofiya A. Bondarenko, Lyudmila Y. Kokaeva, Alla V. Timofeeva, Marina V. Serebryakova, Anna S. Barashkova, Eugene A. Rogozhin, Marina L. Georgieva and Vera S. Sadykova
Molecules 2022, 27(5), 1736; https://doi.org/10.3390/molecules27051736 - 7 Mar 2022
Cited by 14 | Viewed by 3191
Abstract
Features of the biochemical adaptations of alkaliphilic fungi to exist in extreme environments could promote the production of active antibiotic compounds with the potential to control microorganisms, causing infections associated with health care. Thirty-eight alkaliphilic and alkalitolerant Emericellopsis strains (E. alkalina, [...] Read more.
Features of the biochemical adaptations of alkaliphilic fungi to exist in extreme environments could promote the production of active antibiotic compounds with the potential to control microorganisms, causing infections associated with health care. Thirty-eight alkaliphilic and alkalitolerant Emericellopsis strains (E. alkalina, E. cf. maritima, E. cf. terricola, Emericellopsis sp.) isolated from different saline soda soils and belonging to marine, terrestrial, and soda soil ecological clades were investigated for emericellipsin A (EmiA) biosynthesis, an antifungal peptaibol previously described for Emericellopsis alkalina. The analysis of the Emericellopsis sp. strains belonging to marine and terrestrial clades from chloride soils revealed another novel form with a mass of 1032.7 Da, defined by MALDI-TOF Ms/Ms spectrometers, as the EmiA lacked a hydroxyl (dEmiA). EmiA displayed strong inhibitory effects on cell proliferation and viability of HCT 116 cells in a dose- and time-dependent manners and induced apoptosis. Full article
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26 pages, 5141 KiB  
Article
Clinical Relevance of Secreted Small Noncoding RNAs in an Embryo Implantation Potential Prediction at Morula and Blastocyst Development Stages
by Angelika V. Timofeeva, Ivan S. Fedorov, Maria A. Shamina, Vitaliy V. Chagovets, Nataliya P. Makarova, Elena A. Kalinina, Tatiana A. Nazarenko and Gennady T. Sukhikh
Life 2021, 11(12), 1328; https://doi.org/10.3390/life11121328 - 1 Dec 2021
Cited by 8 | Viewed by 3507
Abstract
Despite the improvements in biotechnological approaches and the selection of controlled ovarian hyperstimulation protocols, the resulting pregnancy rate from in vitro fertilization (IVF) protocols still does not exceed 30–40%. In this connection, there is an acute question of the development of a non-invasive, [...] Read more.
Despite the improvements in biotechnological approaches and the selection of controlled ovarian hyperstimulation protocols, the resulting pregnancy rate from in vitro fertilization (IVF) protocols still does not exceed 30–40%. In this connection, there is an acute question of the development of a non-invasive, sensitive, and specific method for assessing the implantation potential of an embryo. A total of 110 subfertile couples were included in the study to undergo the IVF/ICSI program. Obtained embryos for transfer into the uterine cavity of patient cohort 1 (n = 60) and cohort 2 (n = 50) were excellent/good-quality blastocysts, and small noncoding RNA (sncRNA) content in the corresponding spent culture medium samples at the morula stage (n = 43) or at the blastocyst stage (n = 31) was analyzed by deep sequencing followed by qRT-PCR in real time. Two logistic regression models were developed to predict the implantation potential of the embryo with 100% sensitivity and 100% specificity: model 1 at the morula stage, using various combinations of hsa_piR_022258, hsa-let-7i-5p, hsa_piR_000765, hsa_piR_015249, hsa_piR_019122, and hsa_piR_008112, and model 2 at the blastocyst stage, using various combinations of hsa_piR_020497, hsa_piR_008113, hsa-miR-381-3p, hsa_piR_022258, and hsa-let-7a-5p. Protein products of sncRNA potential target genes participate in the selective turnover of proteins through the ubiquitination system and in the organization of the various cell cytoskeleton and nucleoskeleton structures, regulating the activity of the Hippo signaling pathway, which determines the fate specification of the blastomers. Full article
(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)
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20 pages, 18330 KiB  
Article
Unsymmetrical Trifluoromethyl Methoxyphenyl β-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity
by Liliya A. Khamidullina, Igor S. Puzyrev, Gennady L. Burygin, Pavel V. Dorovatovskii, Yan V. Zubavichus, Anna V. Mitrofanova, Victor N. Khrustalev, Tatiana V. Timofeeva, Pavel A. Slepukhin, Polina D. Tobysheva, Alexander V. Pestov, Euro Solari, Alexander G. Tskhovrebov and Valentine G. Nenajdenko
Molecules 2021, 26(21), 6466; https://doi.org/10.3390/molecules26216466 - 26 Oct 2021
Cited by 10 | Viewed by 4359
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Organofluorine Chemistry and Beyond)
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18 pages, 2687 KiB  
Article
Calcium Export from Neurons and Multi-Kinase Signaling Cascades Contribute to Ouabain Neuroprotection in Hyperhomocysteinemia
by Maria A. Ivanova, Arina D. Kokorina, Polina D. Timofeeva, Tatiana V. Karelina, Polina A. Abushik, Julia D. Stepanenko, Dmitry A. Sibarov and Sergei M. Antonov
Biomolecules 2020, 10(8), 1104; https://doi.org/10.3390/biom10081104 - 24 Jul 2020
Cited by 13 | Viewed by 3066
Abstract
Pathological homocysteine (HCY) accumulation in the human plasma, known as hyperhomocysteinemia, exacerbates neurodegenerative diseases because, in the brain, this amino acid acts as a persistent N-methyl-d-aspartate receptor agonist. We studied the effects of 0.1–1 nM ouabain on intracellular Ca2+ [...] Read more.
Pathological homocysteine (HCY) accumulation in the human plasma, known as hyperhomocysteinemia, exacerbates neurodegenerative diseases because, in the brain, this amino acid acts as a persistent N-methyl-d-aspartate receptor agonist. We studied the effects of 0.1–1 nM ouabain on intracellular Ca2+ signaling, mitochondrial inner membrane voltage (φmit), and cell viability in primary cultures of rat cortical neurons in glutamate and HCY neurotoxic insults. In addition, apoptosis-related protein expression and the involvement of some kinases in ouabain-mediated effects were evaluated. In short insults, HCY was less potent than glutamate as a neurotoxic agent and induced a 20% loss of φmit, whereas glutamate caused a 70% decrease of this value. Subnanomolar ouabain exhibited immediate and postponed neuroprotective effects on neurons. (1) Ouabain rapidly reduced the Ca2+ overload of neurons and loss of φmit evoked by glutamate and HCY that rescued neurons in short insults. (2) In prolonged 24 h excitotoxic insults, ouabain prevented neuronal apoptosis, triggering proteinkinase A and proteinkinase C dependent intracellular neuroprotective cascades for HCY, but not for glutamate. We, therefore, demonstrated here the role of PKC and PKA involving pathways in neuronal survival caused by ouabain in hyperhomocysteinemia, which suggests existence of different appropriate pharmacological treatment for hyperhomocysteinemia and glutamate excitotoxicity. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease)
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