Publications by authors named "Mikhail Khvostov"

Article Synopsis
  • The research focuses on finding effective agents against coronaviruses, specifically by synthesizing thiazolo-thiophenes based on usnic acid to inhibit SARS-CoV-2's main protease.
  • Certain modifications of the thiophene groups showed moderate antiviral activity, while others had no effect, with kinetic parameters evaluated for the most promising compound.
  • The most active compound exhibited strong binding to the protease and effective antiviral activity against various SARS-CoV-2 strains, aligning molecular dynamics results with experimental findings.
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Despite the long history of use and the knowledge of the genetics and biochemistry of , problems are still possible in obtaining a soluble form of recombinant proteins in this system. Although, soluble protein can be obtained both in the cytoplasm and in the periplasm of the bacterial cell. The latter is a priority strategy for obtaining soluble proteins.

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  • Type 2 diabetes mellitus (T2DM) is a widespread chronic disease, and despite existing treatments, their side effects necessitate the search for new diabetes drugs.
  • This study tested two compounds, QS-528 and QS-619, on a diet-induced T2DM model in animals, finding that QS-619 effectively lowered blood sugar levels while QS-528 offered liver protection.
  • The research revealed that both compounds activate the free fatty acid receptor-1 (FFAR1), potentially working as full agonists and enhancing insulin and glucose-dependent hormones in mice.
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  • FFAR1 agonists are being researched as potential treatments for type 2 diabetes due to their ability to lower blood sugar levels without causing hypoglycemia.
  • The study involved synthesizing seven new compounds as structural analogs, modifying a previously developed FFA1 receptor agonist to investigate their effects on blood sugar regulation.
  • The novel compounds demonstrated activation of FFAR1 and increased glucose uptake in liver cells without toxicity, with two specific compounds showing significant hypoglycemic effects in glucose tolerance tests on mice.
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  • - Metabolic syndrome involves issues with glucose and lipid metabolism, requiring effective medication for treatment.
  • - Researchers created potential drugs that activate nuclear receptors PPAR-alpha and gamma to improve metabolism, utilizing a specific chemical structure derived from glitazars.
  • - In studies with obese mice suffering from type 2 diabetes, one drug effectively lowered triglycerides and blood sugar, while proving safe for the liver.
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In this study, the mechanochemical synthesis of substituted hydroxyapatite (HA) containing zinc and silicon ions having a chemical formula of CaZn(PO)(SiO)(OH), where x = 0.2, 0.6, 1.

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Article Synopsis
  • In lab tests, shorter alkyl substitutes (C5 and C7) showed a stronger ability to stimulate glucose uptake in liver cells compared to longer ones (C10 and C12), while all derivatives performed better than the original berberine.
  • In animal studies, the C12 derivative improved glucose metabolism in mice over four weeks, yet it also caused liver damage indicators by the end of the experiment.
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Free fatty acid receptor-1 (FFAR1) is one of the possible therapeutic targets in the search for new hepatoprotective drugs. FFAR1 agonists were found to have hypolipidemic, antifibrotic, anti-inflammatory, antiproliferative and antioxidant effects in addition to hypoglycemic action. In this work, we conducted a study of the hepatoprotective effect of the compound QS-528 (previously discovered as an agonist of FFAR1) at doses of 60, 90, 120 and 150 mg/kg on carbon tetrachloride (CCl)-induced liver injury.

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Natural and synthetic coumarins are often considered privileged scaffolds for obtaining pharmacological agents with hypoglycemic activity. Chemical modification of coumarins often leads to antidiabetic agents with greater efficacy. In the present work, twenty monoterpene-substituted 7-hydroxycoumarins were synthesized.

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Article Synopsis
  • Novel 9-N-alkyltetrahydroberberine derivatives were created, and one particular compound with the longest aliphatic chain was chosen for testing on obese mice showing impaired glucose tolerance and non-alcoholic fatty liver disease.
  • After administering this compound at a dose of 15 mg/kg for four weeks, the mice exhibited improved insulin sensitivity, lower fasting glucose levels, and better glucose tolerance during the OGTT.
  • The compound also decreased blood lactate and liver glucokinase levels without any toxic effects observed in the animals, suggesting that this derivative has significant hypoglycemic potential and encourages further research on similar compounds.
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The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used.

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  • Berberine is known for lowering blood glucose levels, but its effectiveness is hampered by a high required dose and poor absorption in the body.
  • Researchers created a new compound derived from berberine, called 9-(hexylamino)-2,3-methylenedioxy-10-methoxyprotoberberine chloride, which shows strong blood sugar-lowering properties.
  • In tests on obese mice with type 2 diabetes, this new compound improved insulin sensitivity, glucose tolerance, reduced body weight and fat, and positively affected liver and pancreatic health.
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Hydroxyapatite (HA), the major mineral component of tooth enamel and natural bones, is a good candidate for bone tissue engineering. Synthetic HA is used for making coatings on metallic implants intended for medical applications. A HA coating renders the implant biocompatible and osteoinductive.

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Nimesulide (NIM, -(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL).

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Physicochemical and pharmacological study of the supramolecular inclusion complexes of the hypotensive drug nifedipine (NF) with the larch polysaccharide arabinogalactan (AG). The NF:AG complexes were obtained and their physicochemical properties were studied. Their hypotensive action and pharmacokinetic profiles were evaluated in rats with normal and elevated arterial blood pressure.

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A series of bornyl derivatives of -(benzyloxy)phenylpropionic acid were prepared, and their hypoglycemic activities were examined by an oral glucose tolerance test in mice. The results of this test revealed two compounds, and , that can reduce the blood level of glucose similarly to reference compound vildagliptin. Both compounds were tested in an experiment on mice with metabolic disorders: the C57BL/6 strain.

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The effect of the natural saponin glycyrrhizic acid (GA) and polysaccharide arabinogalactan (AG) on the transmembrane potential of rat thymocytes was investigated using the potential-sensitive fluorescent probe 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM). Incubation of cells with GA in micellar form resulted in a decrease of the amplitude of observed fluorescence kinetics that points out to a decrease of the transmembrane potential. The proposed mechanism is an increase of membrane ion permeability (passive ion transport) of the plasma cell membrane due to GA incorporation.

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Biodegradable poly(l-lactide)/calcium phosphate composites are promising materials for fabrication of bone fixation implants with improved properties. Multistage compounding was proposed as an efficient method for the preparation of biodegradable poly(l-lactide)/calcium phosphate composites with submicron filler dispersion and mechanical characteristics similar to native bone. The improvement of the characteristics is caused both by the filler itself and by the increase of polymer crystallinity due to the nucleation effect.

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A method of quantitative determination of camphecene, a new anti-influenza agent, in rat blood plasma based on LC-MS/MS was developed, validated and used to study the distribution of the agent between blood cells and blood plasma. The method was validated according to FDA and EMA recommendations in terms of selectivity, linearity, accuracy, precision, recovery, stability and carry-over. Plasma samples were precipitated with methanol followed by the addition of a methanolic solution of 2-adamantylamine hydrochloride (internal standard).

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Pharmaceutical solid dispersions (SD) of curcumin (Cur) with macromolecule polysaccharide arabinogalactan (AG) from wood of Larix sibirica were prepared by mechanical ball milling. The physical properties of the dispersed curcumin mixture in solid state were characterized by scanning electron microscope, differential scanning calorimetry and powder X-ray diffraction studies. These methods showed a strong decrease in the degree of crystallinity of Cur and its transformation to amorphization state, accompanied by the formation of the guest-host type complexes.

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The aim of the present investigation was to enhance the solubility and dissolution of atorvastatin calcium (ATV), a poorly water-soluble drug with larch polysaccharide arabinogalactan (AG) and disodium glycyrrhizate (NaGA) as carriers of drug delivery systems for improving its bioavailability. The interactions of ATV with AG or NaGA were investigated by DSC, XRD, SEM, and NMR techniques. The molecular weights of supramolecular systems-inclusion complexes and micelles-which are the hosts for ATV molecules were measured.

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An amorphous solid dispersion (SD) of curcumin (Cur) with disodium glycyrrhizin (NaGA) was prepared by mechanical ball milling. Curcumin loaded micelles were self-formed by NaGA when SD dissolved in water. The physical properties of Cur SD in solid state were characterized by differential scanning calorimetry, X-ray diffraction studies, and scanning electron microscope.

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In the present work, complexes of simvastatin (SIM) with polysaccharide arabinogalactan (AG) or disodium salt of glycyrrhizin acid (NaGA) have been prepared using mechanochemical technique to improve the solubility of SIM and enhance its oral bioavailability. The interactions of SIM with AG or NaGA were investigated by FTIR, DSC, XRD and SEM. Self-association of SIM in various solvents was investigated by UV/Vis and NMR techniques.

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A fast, selective and sensitive procedure for quantitation of the camphor-based anti-influenza agent camphecene in whole rat blood was developed and validated using dried blood spots and LC-MS/MS. The method was validated according to recommendations of the FDA and EMA in terms of selectivity, linearity, accuracy, precision, recovery, matrix factor, stability, and carry-over. Sample preparation included spotting 20μL of whole blood taken from the tail vein onto the paper, drying and extracting the analyte, followed by evaporation of the solvent and analysis of the residue.

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