87 results on '"Evgeny Chupakhin"'
Search Results
2. 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens
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Elizaveta Rogacheva, Lyudmila Kraeva, Alexey Lukin, Lyubov Vinogradova, Kristina Komarova, Mikhail Chudinov, Maxim Gureev, and Evgeny Chupakhin
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tetrahydropyrazolopyridine ,5-nitrofuran derivatives ,ESKAPE pathogens ,antibacterial testing ,nitroreductase ,flexible docking ,Organic chemistry ,QD241-441 - Abstract
A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPPs) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of the ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(1,3-oxazol-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c] pyridine (13g), which is superior to nitrofurantoin. These results confirmed the benefit of combining a THPP scaffold with a nitrofuran warhead. Certain structure–activity relationships were established in the course of this study which were rationalized by the induced-fit docking experiments in silico.
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- 2023
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3. Synthetic Routes to Approved Drugs Containing a Spirocycle
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Nazar Moshnenko, Alexander Kazantsev, Evgeny Chupakhin, Olga Bakulina, and Dmitry Dar’in
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spirocycles ,three-dimensional ,high-Fsp3 ,spirocyclizations ,cyclodehydration ,ketalization ,Organic chemistry ,QD241-441 - Abstract
The use of spirocycles in drug discovery and medicinal chemistry has been booming in the last two decades. This has clearly translated into the landscape of approved drugs. Among two dozen clinically used medicines containing a spirocycle, 50% have been approved in the 21st century. The present review focuses on the notable synthetic routes to such drugs invented in industry and academia, and is intended to serve as a useful reference source of synthetic as well as general drug information for researchers engaging in the design of new spirocyclic scaffolds for medicinal use or embarking upon analog syntheses inspired by the existing approved drugs.
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- 2023
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4. The Dosidicus gigas Collagen for Scaffold Preparation and Cell Cultivation: Mechanical and Physicochemical Properties, Morphology, Composition and Cell Viability
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Veronika Anohova, Lyudmila Asyakina, Olga Babich, Olga Dikaya, Aleksandr Goikhman, Ksenia Maksimova, Margarita Grechkina, Maxim Korobenkov, Diana Burkova, Aleksandr Barannikov, Anton Narikovich, Evgeny Chupakhin, Anatoly Snigirev, and Sergey Antipov
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collagen scaffolds ,mechanical properties ,physicochemical properties ,morphology ,composition ,cell viability ,Organic chemistry ,QD241-441 - Abstract
Directed formation of the structure of the culture of living cells is the most important task of tissue engineering. New materials for 3D scaffolds of living tissue are critical for the mass adoption of regenerative medicine protocols. In this manuscript, we demonstrate the results of the molecular structure study of collagen from Dosidicus gigas and reveal the possibility of obtaining a thin membrane material. The collagen membrane is characterized by high flexibility and plasticity as well as mechanical strength. The technology of obtaining collagen scaffolds, as well as the results of studies of its mechanical properties, surface morphology, protein composition, and the process of cell proliferation on its surface, are shown in the given manuscript. The investigation of living tissue culture grown on the surface of a collagen scaffold by X-ray tomography on a synchrotron source made it possible to remodel the structure of the extracellular matrix. It was found that the scaffolds obtained from squid collagen are characterized by a high degree of fibril ordering and high surface roughness and provide efficient directed growth of the cell culture. The resulting material provides the formation of the extracellular matrix and is characterized by a short time to living tissue sorption.
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- 2023
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5. Antioxidant and Antimicrobial Activity of Microalgae of the Filinskaya Bay (Baltic Sea)
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Alexandra Shevelyuhina, Olga Babich, Stanislav Sukhikh, Svetlana Ivanova, Egor Kashirskih, Vitaliy Smirnov, Philippe Michaud, and Evgeny Chupakhin
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microalgae ,S. intermedius ,S. obliquus ,proteins ,lipids ,reducing sugars ,Botany ,QK1-989 - Abstract
Microalgae are rich in proteins, carbohydrates, lipids, polyunsaturated fatty acids, vitamins, pigments, enzymes, and other biologically active substances. This research aimed to study the composition and antioxidant and antimicrobial activity of proteins, lipids, and carbohydrates of microalgae found in the Filinskaya Bay of the Kaliningrad region. The chemical composition of Scenedesmus intermedius and Scenedesmus obliquus microalgae biomass was studied. Ultrasound was used to isolate valuable components of microalgae. It was found that microalgae are rich in protein and contain lipids and reducing sugars. To confirm the accuracy of the determination, the protein content was measured using two methods (Kjeldahl and Bradford). Protein content in S. intermedius and S. obliquus microalgae samples did not differ significantly when measured using different methods. Protein extraction by the Kjeldahl method was found to be 63.27% for S. intermedius microalgae samples and 60.11% for S. obliquus microalgae samples. Protein content in S. intermedius samples was 63.46%, compared to 60.07% in S. obliquus samples, as determined by the Bradford method. Lipids were 8.0–8.2 times less abundant than protein in both types of microalgae samples. It was determined that the content of reducing sugars in the samples of the studied microalgae was 5.9 times less than the protein content. The presence of biological activity (antioxidant) in proteins and lipids obtained from biomass samples of the studied microscopic algae was established, which opens up some possibilities for their application in the food, chemical, and pharmaceutical industries (as enzymes, hormones, vitamins, growth substances, antibiotics, and other biologically active compounds).
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- 2022
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6. Bioengineering and Molecular Biology of Miscanthus
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Evgeny Chupakhin, Olga Babich, Stanislav Sukhikh, Svetlana Ivanova, Ekaterina Budenkova, Olga Kalashnikova, Alexander Prosekov, Olga Kriger, and Vyacheslav Dolganyuk
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miscanthus ,genome ,chromosomes ,patterns ,bioengineering ,monolignol ,Technology - Abstract
Miscanthus is a perennial wild plant that is vital for the production of paper and roofing, as well as horticulture and the development of new high-yielding crops in temperate climates. Chromosome-level assembly of the ancient tetraploid genome of miscanthus chromosomes is reported to provide resources that can link its chromosomes to related diploid sorghum and complex polyploid sugarcane. Analysis of Miscanthus sinensis and Miscanthus sacchariflorus showed intense mixing and interspecific hybridization and documented the origin of a high-yielding triploid bioenergetic plant, Miscanthus × giganteus. The Miscanthus genome expands comparative genomics functions to better understand the main abilities of Andropogoneae herbs. Miscanthus × giganteus is widely regarded as a promising lignocellulosic biomass crop due to its high-biomass yield, which does not emit toxic compounds into the environment, and ability to grow in depleted lands. The high production cost of lignocellulosic bioethanol limits its commercialization. The main components that inhibit the enzymatic reactions of fermentation and saccharification are lignin in the cell wall and its by-products released during the pre-treatment stage. One approach to overcoming this barrier could be to genetically modify the genes involved in lignin biosynthesis, manipulating the lignin content and composition of miscanthus.
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- 2022
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7. Assessment of the Resource Potential of Baltic Sea Macroalgae
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Yuliya Kulikova, Stanislav Sukhikh, Olga Kalashnikova, Evgeny Chupakhin, Svetlana Ivanova, Boris Chubarenko, Julia Gorbunova, and Olga Babich
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macroalgae ,biomass ,plastic ,elemental composition ,nutrients ,resource potential ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
The excess biomass of drifting algae and their casting to the Baltic Sea coast imposes a significant environmental burden. The analysis of beach-cast algae showed that the dominant species are macroalgae Ulva sp., Furcellaria lumbricalis, Cladophora sp., and Polysiphonia fucoides. The biomass of Furcellaria and Polysiphonia algae, containing 25.6% and 19.98% sugars, respectively, has the greatest resource potential in terms of obtaining carbohydrates. Fucose, glucose, and galactose were found to be the most common carbohydrates. The lipid content did not exceed 4.3% (2.3–4.3%), while the fatty acid composition was represented by saturated fatty acids (palmitic, stearic, methyloleic, behenic, etc.). The highest content of crude protein was found in samples of macroalgae of the genus Polysiphonia and amounted to 28.2%. A study of the elemental composition of drifting algae revealed that they have a high carbon content (31.3–37.5%) and a low hydrogen (4.96–5.82%), and sulfur (1.75–3.00%) content. Red algal biomass has the most resource potential in terms of biofuel generation, as it has a high number of lipids and proteins that can produce melanoidins during hydrothermal liquefaction, enhancing the fuel yield. The study noted the feasibility of using the biomass of the studied algae taxa to produce polysaccharides and biofuels. The analyses of antioxidant properties, fat content, and fat composition do not provide convincing evidence of the viability of using the aforementioned macroalgae for their production.
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- 2022
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8. Chemical Composition and Content of Biologically Active Substances Found in Cotinus coggygria, Dactylorhiza maculata, Platanthera chlorantha Growing in Various Territories
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Stanislav Sukhikh, Lyudmila Asyakina, Maxim Korobenkov, Liubov Skrypnik, Artem Pungin, Svetlana Ivanova, Timothy Larichev, Viktoria Larina, Olesia Krol, Elena Ulrikh, Evgeny Chupakhin, and Olga Babich
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Cotinus coggygria ,Dactylorhiza maculata ,Platanthera chlorantha ,chemical composition ,organic acids ,vitamins ,Botany ,QK1-989 - Abstract
Medicinal plants (Cotinus coggygria, Dactylorhiza maculata, Platanthera chlorantha) growing in various territories (Kaliningrad, Moscow, and Minsk regions) were the objects of research. This paper presents a study of the chemical composition of these plants. To analyze the qualitative and quantitative composition of biologically active substances, the method of high-performance liquid chromatography was used. Atomic absorption spectrometry was used to study the content of trace elements. The content of organic acids and vitamins was determined by capillary electrophoresis using the Kapel-105/105M capillary electrophoresis system with high negative polarity. Extracts of medicinal plants were obtained on a Soxhlet apparatus using 70% ethanol as an extractant. It was found that among the biologically active substances in the plants under discussion, hyperoside, rutin (C. coggygria), Ferulic acid and Gallic acid (D. maculata), triene hydrocarbon (3,7-Dimethyl-1,3,6-octatriene), unsaturated alcohol (3,7-Dimethyl-2,6-octadien-1-ol), and benzyl acetate (P. chlorantha) prevailed. Samples of these medicinal plants contained trace elements (phosphorus, potassium, calcium, sodium, magnesium, and sulfur) and many aliphatic organic acids (succinic acid, benzoic acid, fumaric acid, citric acid, oxalic acid, and tartaric acid). The largest amount of biologically active substances and secondary metabolites of the studied plants from the Eastern Baltic is associated with climatic and ecological differences from other regions. The composition of these plants determines the potential of their use in feed additives for livestock and poultry as part of measures to improve the quality of livestock products. The use of medicinal plants for the production of feed additives is relevant in terms of improving regional economies, as well as improving the quality of life and nation’s health by providing ecologically clean livestock products.
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- 2021
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9. Methods of Increasing Miscanthus Biomass Yield for Biofuel Production
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Evgeny Chupakhin, Olga Babich, Stanislav Sukhikh, Svetlana Ivanova, Ekaterina Budenkova, Olga Kalashnikova, and Olga Kriger
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Miscanthus ,cellulose ,lignin ,biofuels ,genetic engineering ,Technology - Abstract
The lignocellulosic perennial crop miscanthus, especially Miscanthus × giganteus, is particularly interesting for bioenergy production as it combines high biomass production with low environmental impact. However, there are several varieties that pose a hazard due to susceptibility to disease. This review contains links showing genotype and ecological variability of important characteristics related to yield and biomass composition of miscanthus that may be useful in plant breeding programs to increase bioenergy production. Some clones of Miscanthus × giganteus and Miscanthus sinensis are particularly interesting due to their high biomass production per hectare. Although the compositional requirements for industrial biomass have not been fully defined for the various bioenergy conversion processes, the lignin-rich species Miscanthus × giganteus and Miscanthus sacchariflorus seem to be more suitable for thermochemical conversion processes. At the same time, the species Miscanthus sinensis and some clones of Miscanthus × giganteus with low lignin content are of interest for the biochemical transformation process. The species Miscanthus sacchariflorus is suitable for various bioenergy conversion processes due to its low ash content, so this species is also interesting as a pioneer in breeding programs. Mature miscanthus crops harvested in winter are favored by industrial enterprises to improve efficiency and reduce processing costs. This study can be attributed to other monocotyledonous plants and perennial crops that can be used as feedstock for biofuels.
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- 2021
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10. Antimicrobial Potential of Microorganisms Isolated from the Bottom Sediments of Lake Baikal
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Olga Babich, Margarita Shevchenko, Svetlana Ivanova, Valery Pavsky, Maria Zimina, Svetlana Noskova, Veronika Anohova, Evgeny Chupakhin, and Stanislav Sukhikh
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extremophilic microorganisms ,Lake Baikal ,bottom sediments ,genetic identification ,metabolites ,antimicrobial activity ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Extremophilic microorganisms attract researchers by their unique characteristics, primarily antagonistic ones, acquired in the process of survival in extreme natural conditions. The antimicrobial potential of the metabolites of these microorganisms is quite broad, from the food industry to therapeutic drugs. Microbial mats of Lake Baikal are a source of unique and diverse microorganisms. The study aimed to evaluate the antimicrobial activity of bacterial strains isolated from the bottom sediments of the lake. Using heterotrophic growth conditions, seven bacterial strains were isolated from samples collected in several coastal zones of Lake Baikal. Thisstudy identified both widespread strains of the genera Pseudomonas and Bacillus and rare genera Micrococcus and Acinetobacterrepresentatives. Metabolites of five strains were found to have a broad spectrum of antimicrobial activity. Four large fractions of metabolites of the isolated strains wereidentified. Two peptides of the isolated fractions of metabolites (one is produced by microorganisms of all five isolated strains, another—only by Pseudomonas putida) are low molecular weight oligopeptides. These peptides were proved to be bacteriocins.
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- 2021
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11. Study of the Properties of In Vitro Dactylorhiza maculata (L.) Soó (Family Orchidaceae) Extracts
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Stanislav Sukhikh, Svetlana Noskova, Svetlana Ivanova, Liubov Skrypnik, Artem Pungin, Elena Ulrikh, Evgeny Chupakhin, and Olga Babich
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Dactylorhiza maculata ,extracts ,biologically active substances ,toxicological ,antimicrobial properties ,antioxidant activity ,Botany ,QK1-989 - Abstract
The medicinal plant Dactylorhiza maculata (L.) Soó (family Orchidaceae) is used to treat gastritis, colic, gastrointestinal tract, and bladder diseases. This study aimed to investigate the properties and characteristics of the in vitro Dactylorhiza maculata extract. The recommended parameters for producing Dactylorhiza maculata extract were determined: temperature 60 °C, process duration 60 min, hydro module 1:10. It is recommended to carry out the extraction using an aqueous ethyl alcohol solution with a mass fraction of the parent substance of 70%. It was found that such biologically active substances as rutin, quercetin, 3,3′,4′,5,5′,7-hexahydroxyflavonone, 3,3′,4′,5,5′,7-hexahydroxyflavonone-3-O-glycoside, gallic acid, and ferulic acid were dominant in Dactylorhiza maculata. A high phosphorus content was noted (2410.8 mg/kg dry matter). The studied Dactylorhizamaculata samples contained a large number of organic acids and water-soluble vitamins. The tested extracts were safe in terms of the content of heavy metals, pesticides, aflatoxin B1, and radionuclides, as well as pathogenic and opportunistic microorganisms; the content was significantly lower than the threshold limit values. The studied complex of biologically active substances from Dactylorhiza maculata extract samples had antimicrobial properties. It was found that the antioxidant activity of the samples was 217.89 ± 10.89 mg AA/g (AA—ascorbic acid). The high content of bioactive substances and the antimicrobial and antioxidant properties of Dactylorhizamaculata extract samples determine the application potential of this plant as a substitute for growth stimulants and feed antibiotics in the production of feed additives, aiming to increase the physiological and immune status of livestock and poultry.
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- 2021
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12. Study of the Biologically Active Properties of Medicinal Plant Cotinus coggygria
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Stanislav Sukhikh, Svetlana Noskova, Artem Pungin, Svetlana Ivanova, Liubov Skrypnik, Evgeny Chupakhin, and Olga Babich
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Cotinus coggygria ,biologically active substances ,extracts ,toxicological ,antimicrobial properties ,antioxidant activity ,Botany ,QK1-989 - Abstract
The results of the studies have shown that to obtain an extract of a complex of biologically active substances of Cotinus coggygria, ethyl alcohol (mass fraction of alcohol 70%) with a hydromodule of 1:5 should be used, and the extraction should be carried out for 60 min at a temperature of 60 °C. The investigated plant extracts with the complex of bioactive substances from the Cotinus coggygria leaves and flowers are safe from the point of view of the content of heavy metals, pesticides, aflatoxin B1, radionuclides, as well as pathogenic and opportunistic microorganisms. It has been established that the Cotinus coggygria extract contains rutin, hyperoside, ferulic acid, quercetin, kaempferol, disulphuretin, sulphurein, sulphurein, gallic acid, methyl gallate, pentagalloyl glucose, 3,3′,4′,5,6,7-hexahydroxyflavonone, 3,3′,4′,5,5′,7-hexahydroxyflavonone, 3-O-α-L-rhamnofuranoside, 3,3′,4′,5,5′,7-hexahydroxyflavulium(1+), 7-O-β-D glucopyranoside, and 3,3′,4′,7-tetrahydroxyflavonone. The tested extracts have anticancer, antigenotoxic, and antimicrobial (against E. coli, S. aureus, P. vulgaris, C. albicans, L. mesenteroides) properties. The high antioxidant status of the tested extracts was established; the antioxidant activity of the samples was 145.09 mg AA/g (AA—ascorbic acid).
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- 2021
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13. Enzymatic Hydrolysis of Pretreated Miscanthus Biomass
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Yulia Basova, Maria Smaga, Yakov Masiutin, Olga Kriger, Evgeny Chupakhin, Elena Ulrikh, Ekaterina Budenkova, and Olga Kalashnikova
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Economics, Econometrics and Finance (miscellaneous) ,Industrial and Manufacturing Engineering ,Food Science - Abstract
Forests being mostly non-renewable, miscanthus seems to be a promising alternative energy resource. This study investigates the enzymatic hydrolysis of pretreated miscanthus biomass. The research featured Miscanthus sinensis Strictus biomass. The methods included raw material pretreatment, enzymatic hydrolysis, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) of monosaccharide residues, and nuclear magnetic resonance (1H NMR) spectrometry of non-hydrolyzed lignin. A hammer mill with a particle size of 0.2–0.3 mm proved to be effective for preliminary mechanical processing of miscanthus. This type of treatment provided the maximal yield of carbohydrate-containing biomass (62.33 ± 1.87%). The optimal multi-enzyme composition included Cellulase Ultra obtained from Trichoderma reeseii, xylanase obtained from Thermomyces lanuginosus, and β-gluconase obtained from Myceliophtorafergusii. The fermentation temperature was 50 ± 1°C (72 ± 1 h). At these parameters, the conversion of holocellulose of miscanthus biomass was 96.0 ± 4.8%, and the yield of reducing substances was 97.00 ± 4.85%. The article introduces the optimal enzymatic hydrolysis parameters for pretreating Miscanthus sinensis Strictus biomass as a source of carbohydrate-containing substrates and describes their subsequent use for bacterial cellulose biosynthesis. The carbohydrate composition of hydrolysates included residual lignin, such polysaccharides as glucan and xylan, and various monosaccharides, namely arabinose, xylose, galactose, glucose, and uronic acids. Hydrolyzed miscanthus proved to be an effective renewable and environmentally friendly biodiesel.
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- 2022
14. Evaluation of the Conditions for the Cultivation of Callus Cultures of Hyssopus officinalis Regarding the Yield of Polyphenolic Compounds
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Olga Babich, Stanislav Sukhikh, Artem Pungin, Lidiya Astahova, Evgeny Chupakhin, Daria Belova, Alexander Prosekov, and Svetlana Ivanova
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callus cultures ,medicinal hyssop (Hyssopus officinalis L.) ,medicinal plants ,biologically active substances ,Botany ,QK1-989 - Abstract
The cultivation of plants in the form of callus cultures constitutes a renewable source of secondary plant metabolites. The conditions for the cultivation of callus cultures affect the yield of target compounds. Callus cultures of Hyssopus officinalis were chosen for study. Nutrient media of various compositions were used for Hyssopus officinalis callus culture. For each culture, data on the quantitative contents of saponins, flavonoids and polyphenolic compounds, as well as antioxidant activity, were obtained. It was found that Murashige and Skoog medium supplemented with 1-naphthylacetic acid and kinetin led to the highest yield of secondary metabolites.
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- 2021
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15. Determination of the Qualitative Composition of Biologically Active Substances of Extracts of In Vitro Callus, Cell Suspension, and Root Cultures of the Medicinal Plant Rhaponticum carthamoides
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Lyudmila Asyakina, Svetlana Ivanova, Alexander Prosekov, Lyubov Dyshlyuk, Evgeny Chupakhin, Elena Ulrikh, Olga Babich, and Stanislav Sukhikh
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in vitro callus ,cell suspension and root cultures ,biologically active substances ,ecdysteroids ,HPLC ,1H NMR spectra ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
This work aims to study the qualitative composition of biologically active substance (BAS) extracts in vitro callus, cell suspension, and root cultures of the medicinal plant Rhaponticum carthamoides. The research methodology is based on high-performance liquid chromatography, and 1H nuclear magnetic resonance (NMR) spectra, to study the qualitative and quantitative analysis of BAS. The results of the qualitative composition analysis of the dried biomass extracts of in vitro callus, cell suspension and root cultures showed that the main biologically active substances in the medicinal plant Rhaponticum carthamoides are 2-deoxy-5,20,26-trihydroxyecdyson (7 mg, yield 0.12%), 5,20,26-trihydroxyecdyson 20,22-acetonide (15 mg, yield 0.25%), 2-deoxy-5,20,26-trihydroxyecdyson 20,22-acetonide (6 mg, yield 0.10%), 20,26-dihydroxyecdyson 20,22-acetonidecdyson 20,22-acetonide (5 mg, yield 0.09%), and ecdyson 20,22-acetonide (6 mg, yield 0.10%). In the future, it is planned to study the antimicrobial, antioxidant, and antitumor activity of BAS of extracts of in vitro callus, cell suspension, and root cultures of the medicinal plant Rhaponticum carthamoides, for the production of pharmaceuticals and dietary supplements with antitumor, antimicrobial and antioxidant effects.
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- 2021
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16. SELECTION OF PARAMETERS FOR OBTAINING EXTRACTS OF VALERIANA OFFICINALIS WITH ANTIOXIDANT PROPERIESS
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V.V. Larina, Olga Babich, S Voronova, and Evgeny Chupakhin
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In this work, were obtained various extracts from the root of Valeriana officinalis and was studied their antioxidant activity by three methods, was studied the content of secondary metabolites of a phenolic nature. Biologically active substances were isolated from the extracts individually.
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- 2023
17. The Process of Producing Bioethanol from Delignified Cellulose Isolated from Plants of the Miscanthus Genus
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Olga Kriger, Ekaterina Budenkova, Olga Babich, Stanislav Suhih, Nikolay Patyukov, Yakov Masyutin, Vyacheslav Dolganuk, and Evgeny Chupakhin
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Miscanthus ,delignification ,cellulose fermentation ,ethanol ,microorganism consortium ,biofuel ,Technology ,Biology (General) ,QH301-705.5 - Abstract
Plants of the Miscanthus genus (Miscanthus Anderss.) have a unique index of biomass production in relation to the occupied area. Miscanthus plants can be attributed to promising second-generation raw materials for the production of bioethanol and biofuel. Miscanthus plants are characterized by a high cellulose content. Herein, we report the results of a study on the obtained delignified cellulose with subsequent processing into bioethanol using microbial communities. In the course of the study, the optimal conditions for the delignification of the initial plant material for cellulose were selected. Ethanol with a high degree of conversion was successfully obtained from the isolated delignified cellulose. The article describes the pilot technological scheme for the conversion of Miscanthus plant biomass to bioethanol involving the delignification stages, followed by the conversion of the resulting cellulose into bioethanol by a consortium of microorganisms. As a result of the study, it was found that delignification using trifluoroacetic acid leads to the production of cellulose of high purity. Bioethanol with a yield of 3.1% to 3.4% in terms of the initial amount of biomass was successfully obtained by a microorganism consortium of Saccharomyces cerevisiae M Y-4242/Pachysolen tannophilus Y-3269, and Scheffersomyces stipitis Y-3264.
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- 2020
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18. Natural‐Like Spirocyclic Δ α,β ‐Butenolides Obtained from Diazo Homophthalimides
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Mikhail Krasavin, Vladimir V. Sharoyko, Dmitry Dar'in, Evgeny Chupakhin, and Grigory Kantin
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chemistry.chemical_classification ,Selenocysteine ,010405 organic chemistry ,Stereochemistry ,Thioredoxin reductase ,Organic Chemistry ,Biological activity ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Enzyme ,chemistry ,Diazo ,Cysteine - Abstract
α-Diazo homophotalimides were reacted with various propiolic acids on Rh 2 (esp) 2 catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δ α,β -spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural-like Δ α,β -spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δ α,β -spirobutenolides thus obtained were shown to inhibit thioredoxin reductase, a selenocysteine enzyme target for cancer. Moreover, for the best compound in the series (TrxR IC 50 1.49 ± 0.08 μM), it was shown, using MALDI-TOF mass-spectrometry, that it selectively binds selenocysteine in the presence of a 10-fold excess of cysteine. This validates the new compound as a promising lead for anticancer therapy development.
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- 2021
19. Spirocyclic Motifs in Natural Products
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Evgeny Chupakhin, Olga Babich, Alexander Prosekov, Lyudmila Asyakina, and Mikhail Krasavin
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natural products ,spirocycles ,chemical diversity ,biological activity ,privileged structures ,Organic chemistry ,QD241-441 - Abstract
Spirocyclic motifs are emerging privileged structures for drug discovery. They are also omnipresent in the natural products domain. However, until today, no attempt to analyze the structural diversity of various spirocyclic motifs occurring in natural products and their relative populations with unique compounds reported in the literature has been undertaken. This review aims to fill that void and analyze the diversity of structurally unique natural products containing spirocyclic moieties of various sizes.
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- 2019
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20. Facile Access to Fe(III)-Complexing Cyclic Hydroxamic Acids in a Three-Component Format
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Evgeny Chupakhin, Olga Bakulina, Dmitry Dar’in, and Mikhail Krasavin
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iron complexation ,cyclic hydroxamic acids ,Castagnoli–Cushman reaction ,homophthalic acid ,hydroxylamine acetate ,azeotropic distillation ,cyclodehydration ,Organic chemistry ,QD241-441 - Abstract
Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic constructs for targeted delivery. An earlier described three-component variant of the Castagnoli—Cushman reaction of homophthalic acid (via in situ cyclodehydration to the respective anhydride) was extended to involve hydroxylamine in lieu of the amine component of the reaction. Using hydroxylamine acetate and O-benzylhydroxylamine was key to the success of this transformation due to greater solubility of the reagents in refluxing toluene (compared to hydrochloride salt). The developed protocol was found suitable for multigram-scale syntheses of N-hydroxy- and N-(benzyloxy)tetrahydroisoquinolonic acids. The cyclic hydroxamic acids synthesized in the newly developed format have been tested and shown to be efficient ligands for Fe3+, which makes them suitable candidates for the above-mentioned applications.
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- 2019
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21. Spirocyclizations Involving Oxonium Ylides Derived from Cyclic α-Diazocarbonyl Compounds: An Entry into 6-Oxa-2-azaspiro[4.5]decane Scaffold
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Anna Inyutina, Grigory Kantin, Evgeny Chupakhin, Dmitry Dar'in, Olga Bakulina, and Mikhail Krasavin
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chemistry.chemical_compound ,Scaffold ,chemistry ,010405 organic chemistry ,Organic Chemistry ,Organic chemistry ,Diazo ,Decane ,010402 general chemistry ,Oxonium ion ,01 natural sciences ,Tetrahydrofuran ,0104 chemical sciences - Abstract
New types of cyclic diazo compounds capable of Rh(II)-catalyzed spirocyclizations with tetrahydrofuran have been discovered. The formation of the spirocyclic framework is thought to proceed via the...
- Published
- 2020
22. (E)-3-Arylidene-4-diazopyrrolidine-2,5-diones: Preparation and Use in RhII-Catalyzed X–H Insertion Reactions towards Novel, Medicinally Important Michael Acceptors
- Author
-
Alexander Ivanov, Mikhail Krasavin, Dmitry Dar'in, Martha Gecht, Evgeny Chupakhin, and Grigory Kantin
- Subjects
chemistry.chemical_compound ,chemistry ,Thioredoxin reductase ,Organic Chemistry ,Wittig reaction ,Regioselectivity ,Diazo ,High yielding ,Combinatorial chemistry ,Catalysis - Abstract
The use of readily available 1-aryl-3-arylidenepyrrolidine-2,5-diones in high yielding direct diazo-transfer reactions and subsequent involvement of the resulting diazo compounds in RhII-catalyzed O–H, S–H, and N–H insertion reactions delivered 4-substituted 1-aryl-3-arylidenepyrrolidine-2,5-diones of defined regiochemistry and geometrical configuration. These products are intended to be studied as Michael acceptors capable of inhibiting thioredoxin reductase, a promising cancer target.
- Published
- 2020
23. A Novel Approach to Substituted α-Carbamoyl Phosphonates: Useful Reagents for the Horner–Wadsworth–Emmons Olefination
- Author
-
Evgeny Chupakhin, Mikhail Krasavin, Anna Inyutina, and Dmitry Dar'in
- Subjects
chemistry.chemical_compound ,chemistry ,Reagent ,Organic Chemistry ,Ketene ,Organic chemistry ,Wolff rearrangement - Abstract
α-Carbamoyl phosphonates are useful reagents for the Horner–Wadsworth–Emmons olefination of aldehydes en route to medicinally relevant polysubstituted acrylamides. A new synthetic approach to these reagents has been developed. The methodology relies on the microwave-promoted Wolff rearrangement of α-acyl-α-diazophosphonates with trapping of the ketene intermediate in situ with various amines.
- Published
- 2020
24. Convenient preparation of (E)-3-arylidene-4-diazopyrrolidine-2,5-diones in array format
- Author
-
Evgeny Chupakhin, Grigory Kantin, Mikhail Krasavin, and Dmitry Dar'in
- Subjects
chemistry.chemical_compound ,Chemistry ,Wittig reaction ,Diazo ,General Chemistry ,Combinatorial chemistry - Abstract
A practically convenient synthesis of (E)-3-arylidene-4-diazopyrrolidine-2,5-diones from N-substituted maleimides via the Wittig reaction and the Regitz diazo transfer has been developed. In all 26 cases studied, only one chromatographic purification was required with no need for aqueous workup, which makes this protocol amenable to producing the emerging class of diazo compounds in parallel format.
- Published
- 2021
25. Novel chromeno[2,3-c]pyrroles synthesized via intramolecular rhodium(ii) carbene trapping
- Author
-
Evgeny Chupakhin, Grigory Kantin, Dmitry Dar'in, and Mikhail Krasavin
- Subjects
General Chemistry - Published
- 2022
26. (E)-3-Arylidene-4-diazopyrrolidine-2,5-diones conveniently elaborated into cytotoxic compounds bearing primary sulfonamide and Michael acceptor moieties
- Author
-
Polina Paramonova, Tatiana Sharonova, Stanislav Kalinin, Evgeny Chupakhin, Alexander Bunev, and Mikhail Krasavin
- Subjects
General Chemistry - Published
- 2022
27. Antimicrobial Potential of Microorganisms Isolated from the Bottom Sediments of Lake Baikal
- Author
-
Valery Pavsky, Veronika Anohova, Stanislav Sukhikh, Margarita A. Shevchenko, Evgeny Chupakhin, Svetlana Noskova, Maria Zimina, Olga Babich, and Svetlana Ivanova
- Subjects
Microbiology (medical) ,Microorganism ,genetic identification ,Bacillus ,Micrococcus ,RM1-950 ,Biochemistry ,Microbiology ,Article ,03 medical and health sciences ,bottom sediments ,Bacteriocin ,Pharmacology (medical) ,Microbial mat ,General Pharmacology, Toxicology and Pharmaceutics ,Lake Baikal ,metabolites ,030304 developmental biology ,0303 health sciences ,antimicrobial activity ,biology ,030306 microbiology ,Pseudomonas ,extremophilic microorganisms ,biology.organism_classification ,Antimicrobial ,Pseudomonas putida ,Infectious Diseases ,Therapeutics. Pharmacology - Abstract
Extremophilic microorganisms attract researchers by their unique characteristics, primarily antagonistic ones, acquired in the process of survival in extreme natural conditions. The antimicrobial potential of the metabolites of these microorganisms is quite broad, from the food industry to therapeutic drugs. Microbial mats of Lake Baikal are a source of unique and diverse microorganisms. The study aimed to evaluate the antimicrobial activity of bacterial strains isolated from the bottom sediments of the lake. Using heterotrophic growth conditions, seven bacterial strains were isolated from samples collected in several coastal zones of Lake Baikal. Thisstudy identified both widespread strains of the genera Pseudomonas and Bacillus and rare genera Micrococcus and Acinetobacterrepresentatives. Metabolites of five strains were found to have a broad spectrum of antimicrobial activity. Four large fractions of metabolites of the isolated strains wereidentified. Two peptides of the isolated fractions of metabolites (one is produced by microorganisms of all five isolated strains, another—only by Pseudomonas putida) are low molecular weight oligopeptides. These peptides were proved to be bacteriocins.
- Published
- 2021
28. Study of the Properties of In Vitro Dactylorhiza maculata (L.) Soó (Family Orchidaceae) Extracts
- Author
-
Elena Ulrikh, Evgeny Chupakhin, Svetlana Ivanova, Stanislav Sukhikh, Svetlana Noskova, Artem Pungin, Liubov Skrypnik, and Olga Babich
- Subjects
0106 biological sciences ,Aflatoxin ,extracts ,antimicrobial properties ,Dactylorhiza maculata ,Dactylorhiza ,antioxidant activity ,Plant Science ,01 natural sciences ,Article ,Ferulic acid ,chemistry.chemical_compound ,Dry matter ,Food science ,Gallic acid ,Ecology, Evolution, Behavior and Systematics ,Ecology ,biology ,Botany ,biology.organism_classification ,Antimicrobial ,0104 chemical sciences ,toxicological ,010404 medicinal & biomolecular chemistry ,chemistry ,QK1-989 ,biologically active substances ,Quercetin ,010606 plant biology & botany - Abstract
The medicinal plant Dactylorhiza maculata (L.) Soó (family Orchidaceae) is used to treat gastritis, colic, gastrointestinal tract, and bladder diseases. This study aimed to investigate the properties and characteristics of the in vitro Dactylorhiza maculata extract. The recommended parameters for producing Dactylorhiza maculata extract were determined: temperature 60 °C, process duration 60 min, hydro module 1:10. It is recommended to carry out the extraction using an aqueous ethyl alcohol solution with a mass fraction of the parent substance of 70%. It was found that such biologically active substances as rutin, quercetin, 3,3’,4’,5,5’,7-hexahydroxyflavonone, 3,3’,4’,5,5’,7-hexahydroxyflavonone-3-O-glycoside, gallic acid, and ferulic acid were dominant in Dactylorhiza maculata. A high phosphorus content was noted (2410.8 mg/kg dry matter). The studied Dactylorhiza maculata samples contained a large number of organic acids and water-soluble vitamins. The tested extracts were safe in terms of the content of heavy metals, pesticides, aflatoxin B1, and radionuclides, as well as pathogenic and opportunistic microorganisms, the content was significantly lower than the threshold limit values. The studied complex of biologically active substances from Dactylorhiza maculata extract samples had antimicrobial properties. It was found that the antioxidant activity of the samples was 217.89 ± 10.89 mg AA/g (AA—ascorbic acid). The high content of bioactive substances and the antimicrobial and antioxidant properties of Dactylorhiza maculata extract samples determine the application potential of this plant as a substitute for growth stimulants and feed antibiotics in the production of feed additives, aiming to increase the physiological and immune status of livestock and poultry.
- Published
- 2021
29. Miscanthus plants processing in fuel, energy, chemical and microbiological industries
- Author
-
Olga Babich, Evgeny Chupakhin, Olga Krieger, and Oksana Kozlova
- Subjects
020209 energy ,Biomass ,02 engineering and technology ,Miscanthus ,010501 environmental sciences ,Raw material ,01 natural sciences ,Bioenergy ,0202 electrical engineering, electronic engineering, information engineering ,Ethanol fuel ,0105 earth and related environmental sciences ,bioethanol ,biology ,lcsh:TP368-456 ,biology.organism_classification ,Pulp and paper industry ,cellulose ,lcsh:Food processing and manufacture ,Biofuel ,raw materials ,Environmental science ,processing ,Energy source ,Food Science ,Renewable resource - Abstract
The increasing shortage of fossil hydrocarbon fuel dictates the need to search for and develop alternative energy sources, including plant biomass. This paper is devoted to the study of the Miscanthus plants biomass potential and the analysis of technologies of its processing into products targeted at bioenergy, chemistry, and microbiology. Miscanthus is a promising renewable raw material to replace wood raw materials for the production of chemical, fuel, energy, and microbiological industries. Miscanthus is characterised by highly productive (up to 40 tons per one hectare of dry matter) C4-photosynthesis. Dry Miscanthus contains 47.1–49.7% carbon, 5.38–5.92% hydrogen, and 41.4–44.6% oxygen. The mineral composition includes K, Cl, N and S, which influence the processes occurring during biomass combustion. The total amount of extractives per dry substance lies in the range of 0.3–2.2 % for different extraction reagents. Miscanthus has optimal properties as an energy source. Miscanthus × giganteus pellets showed the energy value of about 29 kJ/g. For the bioconversion of plants into bioethanol, it is advisable to carry out simultaneous saccharification and fermentation, thus reducing the duration of process steps and energy costs. Miscanthus cellulose is of high quality and can be used for the synthesis of new products. Further research will focus on the selection of rational parameters for processing miscanthus biomass into products with improved physical and chemical characteristics: bioethanol, pellets, industrial cellulose, bacterial cellulose, carbohydrate substrate.
- Published
- 2019
30. Three-Component Castagnoli–Cushman Reaction of 3-Arylglutaconic Acids with Aromatic Aldehydes and Amines Delivers Rare 4,6-Diaryl-1,6-dihydropyridin-2(3H)-ones
- Author
-
Evgeny Chupakhin, Mikhail Krasavin, Andrei Firsov, Dmitry Dar'in, and Olga Bakulina
- Subjects
Chemotype ,010405 organic chemistry ,Component (thermodynamics) ,Chemistry ,Stereochemistry ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Bioactive compound ,0104 chemical sciences ,chemistry.chemical_compound ,Domain (ring theory) ,Physical and Theoretical Chemistry - Abstract
Attempted use of 3-arylglutaconic acids in the three-component version of the Castagnoli-Cushman reaction with amines and aromatic aldehydes resulted in an unexpected formation of 4,6-diaryl 1,6-dihydropyridine-2(3 H)-ones. These are of interest as representatives of a rare heterocyclic chemotype for de novo biological investigation. Alternatively, these compounds can be oxidized into their 2-pyridone counterparts, stereoselectively reduced to give cis-configured 4,6-diaryl 2-piperidones, or isomerized to 5,6-dihydropyridin-2(1 H)-ones. All the three scaffolds are well represented in the bioactive compound domain.
- Published
- 2019
31. Study of the Biologically Active Properties of Medicinal Plant
- Author
-
Liubov Skrypnik, Stanislav Sukhikh, Evgeny Chupakhin, Artem Pungin, Olga Babich, Svetlana Ivanova, and Svetlana Noskova
- Subjects
0106 biological sciences ,extracts ,antimicrobial properties ,Hyperoside ,antioxidant activity ,Plant Science ,01 natural sciences ,Article ,Ferulic acid ,03 medical and health sciences ,chemistry.chemical_compound ,Rutin ,Cotinus coggygria ,Gallic acid ,Methyl gallate ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,Ecology ,Traditional medicine ,biology ,Botany ,biology.organism_classification ,toxicological ,Cotinus ,chemistry ,QK1-989 ,biologically active substances ,Quercetin ,Kaempferol ,010606 plant biology & botany - Abstract
The results of the studies have shown that to obtain an extract of a complex of biologically active substances of Cotinus coggygria, ethyl alcohol (mass fraction of alcohol 70%) with a hydromodule of 1:5 should be used, and the extraction should be carried out for 60 min at a temperature of 60 °C. The investigated plant extracts with the complex of bioactive substances from the Cotinus coggygria leaves and flowers are safe from the point of view of the content of heavy metals, pesticides, aflatoxin B1, radionuclides, as well as pathogenic and opportunistic microorganisms. It has been established that the Cotinus coggygria extract contains rutin, hyperoside, ferulic acid, quercetin, kaempferol, disulphuretin, sulphurein, sulphurein, gallic acid, methyl gallate, pentagalloyl glucose, 3,3′,4′,5,6,7-hexahydroxyflavonone, 3,3′,4′,5,5′,7-hexahydroxyflavonone, 3-O-α-L-rhamnofuranoside, 3,3′,4′,5,5′,7-hexahydroxyflavulium(1+), 7-O-β-D glucopyranoside, and 3,3′,4′,7-tetrahydroxyflavonone. The tested extracts have anticancer, antigenotoxic, and antimicrobial (against E. coli, S. aureus, P. vulgaris, C. albicans, L. mesenteroides) properties. The high antioxidant status of the tested extracts was established, the antioxidant activity of the samples was 145.09 mg AA/g (AA—ascorbic acid).
- Published
- 2021
32. Natural-Like Spirocyclic Δ
- Author
-
Dmitry, Dar'in, Grigory, Kantin, Evgeny, Chupakhin, Vladimir, Sharoyko, and Mikhail, Krasavin
- Abstract
α-Diazo homophotalimides were reacted with various propiolic acids on Rh
- Published
- 2021
33. Thioredoxin reductase inhibitors: updated patent review (2017-present)
- Author
-
Mikhail Krasavin and Evgeny Chupakhin
- Subjects
Thioredoxin-Disulfide Reductase ,Thioredoxin reductase ,Glutathione reductase ,Antineoplastic Agents ,medicine.disease_cause ,01 natural sciences ,Patents as Topic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Thioredoxins ,Drug Development ,Neoplasms ,Drug Discovery ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,Selenocysteine ,Neurodegeneration ,General Medicine ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Oxidative Stress ,Enzyme ,chemistry ,Biochemistry ,030220 oncology & carcinogenesis ,Thioredoxin ,Oxidative stress - Abstract
Introduction: Thioredoxin reductase (TrxR) is a selenocysteine-containing enzyme which is responsible - as a part of the thioredoxin system - for maintaining redox homeostasis in cells. It is upregulated in cancerous state as a defense against oxidative stress. TrxR has been mostly considered an anticancer drug target although it has applications in other therapeutic areas such as neurodegeneration, inflammation, microbial infections, and neonatal hyperoxic lung injury.Areas covered: The present review covers the patent literature that appeared in the period 2017-2020, i.e. since the publication of the previous expert opinion patent review on TrxR inhibitors. The recent additions to the following traditional classes of inhibitors are discussed: metal complexes, Michael acceptors as well as arsenic and selenium compounds. At the same time, a novel group of nitro (hetero)aromatic compounds have emerged which likely acts via covalent inhibition mechanism. Several miscellaneous chemotypes are grouped under Miscellaneous subsection.Expert opinion: While specificity over glutathione reductase is achieved easily, TrxR is still moving toward the later stages of development at a very slow rate. Michael acceptors, particularly based on TRXR substrate-mimicking scaffolds, are gaining impetus and so are dual and hybrid compounds. The development prospects of the emerging nitro (hetero)aromatic chemotypes remain uncertain.
- Published
- 2021
34. Plants of the Russian Federation pharmacopeia: an unexhausted natural products research opportunity?
- Author
-
Evgeny Chupakhin, Mikhail Krasavin, Lyudmila Asyakina, Alexander Prosekov, Maxim Gureev, and Olga Babich
- Subjects
Biological Products ,Plants, Medicinal ,Traditional medicine ,010405 organic chemistry ,fungi ,Organic Chemistry ,virus diseases ,food and beverages ,Plant Science ,01 natural sciences ,Biochemistry ,Natural (archaeology) ,0104 chemical sciences ,Analytical Chemistry ,Russia ,010404 medicinal & biomolecular chemistry ,Geography ,Russian federation ,Medicinal plants ,geographic locations - Abstract
32 medicinal plants that are unique to the Russian Pharmacopeia have 693 isolated natural products associated with them (an average of 21.66 compounds per plant). This is in contrast to the US Pharmacopeia plants that have delivered 2366 known natural products (an average of 42.25 compounds per plant).
- Published
- 2020
35. The Castagnoli-Cushman reaction in a three-component format
- Author
-
Evgeny Chupakhin, Mikhail Krasavin, and Dmitry Dar'in
- Subjects
chemistry.chemical_classification ,Homophthalic acid ,010405 organic chemistry ,Component (thermodynamics) ,Organic Chemistry ,One-pot synthesis ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Aldehyde ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Reagent ,Drug Discovery ,Organic chemistry ,Amine gas treating - Abstract
The first example of the Castagnoli-Cushman reaction of homophthalic acid with an amine and an aldehyde conducted in a three-component format is reported. This new protocol employs no dehydrating agents and, unlike the traditional Castagnoli-Cushman reaction of homophthalic anhydride, allows simultaneous mixing of all three reagents and provides good to excellent yields of trans-configured tetrahydroisoquinolonic acids.
- Published
- 2018
36. Achievements in the synthesis of cyclooctynes for ring strain-promoted [3+2] azide-alkyne cycloaddition
- Author
-
Evgeny Chupakhin and Mikhail Krasavin
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Alkyne ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Cycloaddition ,0104 chemical sciences ,Cellular engineering ,Ring strain ,chemistry.chemical_compound ,chemistry ,Reactivity (chemistry) ,Azide - Abstract
The aim of this review is to present the entire range of cyclooctynes that are currently known in the literature. We provide a generalized and systematic overview of methods for their synthesis and consider the applications of cyclooctynes for the purposes of molecular biology and cellular engineering. The importance of cyclooctynes for [3+2] azide-alkyne cycloaddition is demonstrated, as the high reactivity of cyclooctynes allows to perform this reaction under mild conditions without a catalyst.
- Published
- 2018
37. Facile entry into the 1H-pyrrolo[3,4-b]indolizine-1,3(2H)-dione scaffold via intramolecular Rh(II) carbene trapping
- Author
-
Evgeny Chupakhin, Mikhail Krasavin, Dmitry Dar'in, and Olga Bakulina
- Subjects
Organic Chemistry ,Trapping ,Biochemistry ,Fluorescence ,Medicinal chemistry ,Pyrrolidine ,chemistry.chemical_compound ,Nitrogen atom ,chemistry ,Intramolecular force ,Drug Discovery ,Reactivity (chemistry) ,Indolizine ,Carbene - Abstract
An unusual reactivity of Rh(II) carbenes generated from (E)-3-(2-pyridylmethylene)-4-diazopyrrolidine-2,5-diones was discovered which led to a novel type of fluorescent annelated indolizines (X-ray confirmed structure). The reaction was found to be insensitive to substitution pattern at pyrrolidine nitrogen atom and delivered a series of nine novel indolizines in 74–94% yields. Photophysical properties of obtained indolizines were investigated, which proved them to be blue or green luminophores with absolute quantum yields up to 13.8%. The latter strongly depended on substitution pattern at pyrrolidine nitrogen atom.
- Published
- 2021
38. Skeletal Diversity in Combinatorial Fashion: A New Format for the Castagnoli–Cushman Reaction
- Author
-
Evgeny Chupakhin, Olga Bakulina, Mikhail Krasavin, Anastasia Lepikhina, and Dmitry Dar'in
- Subjects
Aldehydes ,Lactams ,Molecular Structure ,Combinatorial Chemistry Techniques ,010405 organic chemistry ,Chemistry ,Acetic Anhydrides ,Chemistry Techniques, Synthetic ,General Chemistry ,General Medicine ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Acetic anhydride ,chemistry.chemical_compound ,Cyclization ,Molecule ,Organic chemistry ,Dicarboxylic Acids ,Amines - Abstract
A new format for the Castagnoli–Cushman reaction of structurally diverse dicarboxylic acids, amines, and aldehydes in the presence of acetic anhydride as dehydrating agent is described. The reaction is distinctly amenable to parallel format: the combinatorial array of 180 reactions delivered 157 products of >85% purity without chromatographic purification (of this number, 143 compounds had >94% purity). The new method offers a convenient preparation of the skeletally and peripherally diverse, lead- and druglike γ- and δ-lactam carboxylic acids with high diastereoselectivity in combinatorial fashion.
- Published
- 2017
39. Efficient cyclodehydration of dicarboxylic acids with oxalyl chloride
- Author
-
Evgeny Chupakhin, Dmitry Dar'in, Grigory Kantin, and Mikhail Krasavin
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,Dicarboxylic acid ,chemistry ,Oxalyl chloride ,Reagent ,Drug Discovery ,Organic chemistry - Abstract
Literature examples illustrating the use of oxalyl chloride to prepare dicarboxylic acid anhydrides are surprisingly limited. At the same time, we have discovered a method involving the use of this readily available reagent which allowed the preparation of novel cyclic anhydrides where other, more conventional, methods had failed. Herein, we demonstrate that the method is applicable to a wide diversity of substrates, delivers good to excellent yields of cyclic anhydrides without chromatographic purification and can be considered a synthetic tool of choice whenever dicarboxylic acid cyclodehydration is required.
- Published
- 2017
40. Evaluation of the Conditions for the Cultivation of Callus Cultures of Hyssopus officinalis Regarding the Yield of Polyphenolic Compounds
- Author
-
Evgeny Chupakhin, Artem Pungin, Alexander Prosekov, Daria Belova, Lidiya Astahova, Svetlana Ivanova, Olga Babich, and Stanislav Sukhikh
- Subjects
0106 biological sciences ,Antioxidant ,medicine.medical_treatment ,Plant Science ,01 natural sciences ,callus cultures ,03 medical and health sciences ,chemistry.chemical_compound ,Murashige and Skoog medium ,medicine ,Medicinal plants ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,medicinal hyssop (Hyssopus officinalis L.) ,0303 health sciences ,Ecology ,Brief Report ,fungi ,Botany ,food and beverages ,musculoskeletal system ,Horticulture ,chemistry ,Polyphenol ,QK1-989 ,Callus ,Yield (chemistry) ,biologically active substances ,Kinetin ,Hyssopus officinalis ,medicinal plants ,010606 plant biology & botany - Abstract
The cultivation of plants in the form of callus cultures constitutes a renewable source of secondary plant metabolites. The conditions for the cultivation of callus cultures affect the yield of target compounds. Callus cultures of Hyssopus officinalis were chosen for study. Nutrient media of various compositions were used for Hyssopus officinalis callus culture. For each culture, data on the quantitative contents of saponins, flavonoids and polyphenolic compounds, as well as antioxidant activity, were obtained. It was found that Murashige and Skoog medium supplemented with 1-naphthylacetic acid and kinetin led to the highest yield of secondary metabolites.
- Published
- 2021
41. 1,1′-Carbonyldiimidazole as a cyclodehydrating agent for the Castagnoli–Cushman reaction of dicarboxylic acids and imines
- Author
-
Olga Bakulina, Mikhail Krasavin, Evgeny Chupakhin, and Dmitry Dar'in
- Subjects
Acylation ,Acetic anhydride ,chemistry.chemical_compound ,chemistry ,010405 organic chemistry ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Carbonyldiimidazole ,0104 chemical sciences - Abstract
A novel protocol for the Castagnoli–Cushman reaction of dicarboxylic acids and imines comprises the use of 1,1′-carbonyldiimidazole as the cyclodehydrating agent to in situ produce the intermediate anhydrides. In contrast to previously developed procedure involving the use of acetic anhydride, the current protocol allows one to utilize substrates prone to acylation or acid-promoted transformations, which significantly broadens the reaction scope of lactams to be obtained.
- Published
- 2019
42. Detection of Mutations in Mitochondrial DNA by Droplet Digital PCR
- Author
-
Konstantin E. Orishchenko, Yury Yu. Ilinsky, I. O. Mazunin, Evgenii A. Lunev, Evgeny Chupakhin, and J. K. Sofronova
- Subjects
0301 basic medicine ,Genetics ,Mutation ,Mitochondrial DNA ,Mitochondrial disease ,Mutant ,DNA Mutational Analysis ,General Medicine ,Biology ,Mitochondrion ,medicine.disease ,medicine.disease_cause ,Biochemistry ,DNA, Mitochondrial ,Polymerase Chain Reaction ,eye diseases ,Heteroplasmy ,03 medical and health sciences ,030104 developmental biology ,medicine ,Animals ,Humans ,Digital polymerase chain reaction ,Allele - Abstract
Mutations in mitochondrial DNA (mtDNA) may result in various pathological processes. Detection of mutant mtDNAs is a problem for diagnostic practice that is complicated by heteroplasmy – a phenomenon of the inferring presence of at least two allelic variants of the mitochondrial genome. Also, the level of heteroplasmy largely determines the profile and severity of clinical manifestations. Here we discuss detection of mutations in heteroplasmic mtDNA using up-todate methods that have not yet been introduced as routine clinical assays. These methods can be used for detecting mutations in mtDNA to verify diagnosis of “mitochondrial disease”, studying dynamics of mutant mtDNA in body tissues of patients, as well as investigating structural features of mtDNAs. Original data on allele-specific discrimination of m.11778G>A mutation by droplet digital PCR are presented, which demonstrate an opportunity for simultaneous detection and quantitative assessment of mutations in mtDNAs.
- Published
- 2016
43. Spirocyclic Motifs in Natural Products
- Author
-
Alexander Prosekov, Evgeny Chupakhin, Mikhail Krasavin, Lyudmila Asyakina, and Olga Babich
- Subjects
natural products ,Pharmaceutical Science ,Structural diversity ,biological activity ,Review ,Computational biology ,spirocycles ,Biology ,010402 general chemistry ,01 natural sciences ,Analytical Chemistry ,lcsh:QD241-441 ,Structure-Activity Relationship ,lcsh:Organic chemistry ,Drug Discovery ,Spiro Compounds ,Physical and Theoretical Chemistry ,chemical diversity ,privileged structures ,Biological Products ,010405 organic chemistry ,Drug discovery ,Organic Chemistry ,0104 chemical sciences ,Models, Chemical ,Chemistry (miscellaneous) ,Chemical diversity ,Molecular Medicine ,human activities - Abstract
Spirocyclic motifs are emerging privileged structures for drug discovery. They are also omnipresent in the natural products domain. However, until today, no attempt to analyze the structural diversity of various spirocyclic motifs occurring in natural products and their relative populations with unique compounds reported in the literature has been undertaken. This review aims to fill that void and analyze the diversity of structurally unique natural products containing spirocyclic moieties of various sizes.
- Published
- 2019
44. Facile Access to Fe(III)-Complexing Cyclic Hydroxamic Acids in a Three-Component Format
- Author
-
Dmitry Dar'in, Mikhail Krasavin, Evgeny Chupakhin, and Olga Bakulina
- Subjects
Hydrochloride ,cyclic hydroxamic acids ,hydroxylamine acetate ,Siderophores ,Pharmaceutical Science ,Salt (chemistry) ,Hydroxamic Acids ,Ferric Compounds ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,chemistry.chemical_compound ,Hydroxylamine ,azeotropic distillation ,lcsh:Organic chemistry ,Coordination Complexes ,Drug Discovery ,Physical and Theoretical Chemistry ,Solubility ,chemistry.chemical_classification ,Homophthalic acid ,fungi ,Organic Chemistry ,food and beverages ,iron complexation ,homophthalic acid ,Combinatorial chemistry ,Toluene ,Castagnoli–Cushman reaction ,chemistry ,Chemistry (miscellaneous) ,Reagent ,cyclodehydration ,Molecular Medicine ,Amine gas treating - Abstract
Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic constructs for targeted delivery. An earlier described three-component variant of the Castagnoli&mdash, Cushman reaction of homophthalic acid (via in situ cyclodehydration to the respective anhydride) was extended to involve hydroxylamine in lieu of the amine component of the reaction. Using hydroxylamine acetate and O-benzylhydroxylamine was key to the success of this transformation due to greater solubility of the reagents in refluxing toluene (compared to hydrochloride salt). The developed protocol was found suitable for multigram-scale syntheses of N-hydroxy- and N-(benzyloxy)tetrahydroisoquinolonic acids. The cyclic hydroxamic acids synthesized in the newly developed format have been tested and shown to be efficient ligands for Fe3+, which makes them suitable candidates for the above-mentioned applications.
- Published
- 2019
45. The Process of Producing Bioethanol from Delignified Cellulose Isolated from Plants of the Miscanthus Genus.
- Author
-
Kriger, Olga, Budenkova, Ekaterina, Babich, Olga, Suhih, Stanislav, Patyukov, Nikolay, Masyutin, Yakov, Dolganuk, Vyacheslav, and Chupakhin, Evgeny
- Subjects
PLANT biomass ,MISCANTHUS ,BIOMASS production ,ETHANOL as fuel ,RAW materials ,TRIFLUOROACETIC acid ,CELLULOSE ,LIGNOCELLULOSE - Abstract
Plants of the Miscanthus genus (Miscanthus Anderss.) have a unique index of biomass production in relation to the occupied area. Miscanthus plants can be attributed to promising second-generation raw materials for the production of bioethanol and biofuel. Miscanthus plants are characterized by a high cellulose content. Herein, we report the results of a study on the obtained delignified cellulose with subsequent processing into bioethanol using microbial communities. In the course of the study, the optimal conditions for the delignification of the initial plant material for cellulose were selected. Ethanol with a high degree of conversion was successfully obtained from the isolated delignified cellulose. The article describes the pilot technological scheme for the conversion of Miscanthus plant biomass to bioethanol involving the delignification stages, followed by the conversion of the resulting cellulose into bioethanol by a consortium of microorganisms. As a result of the study, it was found that delignification using trifluoroacetic acid leads to the production of cellulose of high purity. Bioethanol with a yield of 3.1% to 3.4% in terms of the initial amount of biomass was successfully obtained by a microorganism consortium of Saccharomyces cerevisiae M Y-4242/Pachysolen tannophilus Y-3269, and Scheffersomyces stipitis Y-3264. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
46. 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens.
- Author
-
Rogacheva, Elizaveta, Kraeva, Lyudmila, Lukin, Alexey, Vinogradova, Lyubov, Komarova, Kristina, Chudinov, Mikhail, Gureev, Maxim, and Chupakhin, Evgeny
- Subjects
LEAD compounds ,STRUCTURE-activity relationships ,PROTEIN-ligand interactions ,PATHOGENIC microorganisms ,CURRICULUM - Abstract
A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPPs) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of the ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(1,3-oxazol-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c] pyridine (13g), which is superior to nitrofurantoin. These results confirmed the benefit of combining a THPP scaffold with a nitrofuran warhead. Certain structure–activity relationships were established in the course of this study which were rationalized by the induced-fit docking experiments in silico. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
47. Synthetic Routes to Approved Drugs Containing a Spirocycle †.
- Author
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Moshnenko, Nazar, Kazantsev, Alexander, Chupakhin, Evgeny, Bakulina, Olga, and Dar'in, Dmitry
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DRUG discovery ,PHARMACEUTICAL chemistry ,CLAISEN condensation ,REFERENCE sources ,TWENTY-first century ,SYNTHETIC drugs - Abstract
The use of spirocycles in drug discovery and medicinal chemistry has been booming in the last two decades. This has clearly translated into the landscape of approved drugs. Among two dozen clinically used medicines containing a spirocycle, 50% have been approved in the 21st century. The present review focuses on the notable synthetic routes to such drugs invented in industry and academia, and is intended to serve as a useful reference source of synthetic as well as general drug information for researchers engaging in the design of new spirocyclic scaffolds for medicinal use or embarking upon analog syntheses inspired by the existing approved drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
48. The Dosidicus gigas Collagen for Scaffold Preparation and Cell Cultivation: Mechanical and Physicochemical Properties, Morphology, Composition and Cell Viability.
- Author
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Anohova, Veronika, Asyakina, Lyudmila, Babich, Olga, Dikaya, Olga, Goikhman, Aleksandr, Maksimova, Ksenia, Grechkina, Margarita, Korobenkov, Maxim, Burkova, Diana, Barannikov, Aleksandr, Narikovich, Anton, Chupakhin, Evgeny, Snigirev, Anatoly, and Antipov, Sergey
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TISSUE scaffolds ,CELL survival ,COLLAGEN ,TISSUE culture ,EXTRACELLULAR matrix ,MORPHOLOGY - Abstract
Directed formation of the structure of the culture of living cells is the most important task of tissue engineering. New materials for 3D scaffolds of living tissue are critical for the mass adoption of regenerative medicine protocols. In this manuscript, we demonstrate the results of the molecular structure study of collagen from Dosidicus gigas and reveal the possibility of obtaining a thin membrane material. The collagen membrane is characterized by high flexibility and plasticity as well as mechanical strength. The technology of obtaining collagen scaffolds, as well as the results of studies of its mechanical properties, surface morphology, protein composition, and the process of cell proliferation on its surface, are shown in the given manuscript. The investigation of living tissue culture grown on the surface of a collagen scaffold by X-ray tomography on a synchrotron source made it possible to remodel the structure of the extracellular matrix. It was found that the scaffolds obtained from squid collagen are characterized by a high degree of fibril ordering and high surface roughness and provide efficient directed growth of the cell culture. The resulting material provides the formation of the extracellular matrix and is characterized by a short time to living tissue sorption. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
49. Acknowledgment to the Reviewers of Molecules in 2022.
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MOLECULES ,SCHOLARLY publishing - Abstract
Regardless of whether the articles they examined were ultimately published, the editors would like to express their appreciation and thank the following reviewers for the time and dedication that they have shown I Molecules i olely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). Thanks to the efforts of our reviewers in 2022, the median time to first decision was 14 days and the median time to publication was 34 days. I Molecules i was able to uphold its high standards for published papers due to the outstanding efforts of our reviewers. [Extracted from the article]
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- 2023
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50. Antioxidant and Antimicrobial Activity of Microalgae of the Filinskaya Bay (Baltic Sea).
- Author
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Shevelyuhina, Alexandra, Babich, Olga, Sukhikh, Stanislav, Ivanova, Svetlana, Kashirskih, Egor, Smirnov, Vitaliy, Michaud, Philippe, and Chupakhin, Evgeny
- Subjects
SCENEDESMUS obliquus ,MICROALGAE ,BIOACTIVE compounds ,ANTI-infective agents ,GROWTH factors ,UNSATURATED fatty acids - Abstract
Microalgae are rich in proteins, carbohydrates, lipids, polyunsaturated fatty acids, vitamins, pigments, enzymes, and other biologically active substances. This research aimed to study the composition and antioxidant and antimicrobial activity of proteins, lipids, and carbohydrates of microalgae found in the Filinskaya Bay of the Kaliningrad region. The chemical composition of Scenedesmus intermedius and Scenedesmus obliquus microalgae biomass was studied. Ultrasound was used to isolate valuable components of microalgae. It was found that microalgae are rich in protein and contain lipids and reducing sugars. To confirm the accuracy of the determination, the protein content was measured using two methods (Kjeldahl and Bradford). Protein content in S. intermedius and S. obliquus microalgae samples did not differ significantly when measured using different methods. Protein extraction by the Kjeldahl method was found to be 63.27% for S. intermedius microalgae samples and 60.11% for S. obliquus microalgae samples. Protein content in S. intermedius samples was 63.46%, compared to 60.07% in S. obliquus samples, as determined by the Bradford method. Lipids were 8.0–8.2 times less abundant than protein in both types of microalgae samples. It was determined that the content of reducing sugars in the samples of the studied microalgae was 5.9 times less than the protein content. The presence of biological activity (antioxidant) in proteins and lipids obtained from biomass samples of the studied microscopic algae was established, which opens up some possibilities for their application in the food, chemical, and pharmaceutical industries (as enzymes, hormones, vitamins, growth substances, antibiotics, and other biologically active compounds). [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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