Synthesis and Assessment of Antiplatelet and Antithrombotic Activity of 4-Amino-Substituted 5-Oxoproline Amides and Peptides.

Venous thromboembolism is a serious problem because it significantly increases the risk of developing vascular complications in elderly patients with obesity or immobilization, cancer, and many other diseases. Thus, there is a need to study new therapeutic strategies, including new medicinal agents for the efficient and safe correction of thrombus disorders. In this work, we have synthesized a number of new amides and peptides of 4-amino-5-oxoprolines and studied their antiplatelet and antithrombotic activity in experiments in vitro and in vivo.

[Synergistic effects of GABA and hypoglycemic drugs].

Diabetes mellitus (DM) is the leading cause of premature death and disability. Despite a significant number of drugs, the effectiveness of therapy aimed at normalizing the level of glycemia and preventing complications does not fully satisfy doctors and patients. Therefore, the search for new approaches for the prevention and treatment of DM and its complications continues.

The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats.

The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synthase (iNOS). AAI induced a pronounced decrease in the contractile function of the myocardium during exercise tests (load by volume, test for adrenoreactivity, isometric exercise), caused mitochondrial dysfunction and increased processes of lipid peroxidation (LPO) in heart cells. A decrease in NO production during iNOS inhibition and AAI improved the respiratory function of mitochondria, a decreased the level of LPO products, and increased mitochondrial superoxide dismutase activity of heart cells.

Solid herbal extract of L. improves morphofunctional condition of rats' myocardium in chronic alcohol intoxication.

Background And Aim: Chronic alcohol intoxication (CAI) induces heart damage. One of the promising ways of its treatment involves the administration of herbal medicinal products. The purpose of this study was to explore the effect of solid herbal extract of Primula veris L.

Synthesis, structure, and biological activity of 4-hetaryl-2-pyrrolidones containing a pyrazole ring.

Unlabelled: Single diastereomers of 4-hetaryl-2-pyrrolidone-3(5)-carbo- and 2-[4-hetaryl-2-pyrrolidon-1-yl]acetohydrazides were used in reactions with 2,4-pentanedione, providing (3,4)-3-, (4,5)-5-(3,5-dimethyl-1-pyrazole-1-carbonyl)- and 1-[2-(3,5-dimethyl-1-pyrazol-1-yl)-2-oxoethyl]-4-hetaryl-2-pyrrolidones. The structures of the synthesized compounds were confirmed by spectral methods and X-ray structural analysis. Some of the obtained compounds were shown to possess nootropic and anxiolytic activity.

Pyrimidine thioethers: A novel class of antidepressant agents, endowed with anxiolytic, performance enhancing and nootropic activity.

A series of new pyrimidine thioethers, recognized as the key intermediates in the synthesis of S-DABO antivirals, were prepared and evaluated both in vivo and in silico. The purpose of this evaluation was to find novel structural analogues of the known antihypoxic drug Isothiobarbamine endowed with improved pharmacological profile. The in vivo studies led to the identification of compounds 5c, 5e, and 5f endowed with antidepressant/anxiolytic, performance enhancing, and nootropic properties.

[Changes in the psychoemotional state under the influence of derivatives of neuroactive amino acids of rats after chronic alcohol intoxication].

Objective: To study an effect of neuroactive amino acids derivatives glufimet and mefargin on the psychoemotional state of rats after chronic alcohol intoxication (CAI).

Material And Methods: The study was carried out on 10-month-old female Wistar rats. CAI was modeled by replacing drinking water with a 10% solution of ethyl alcohol sweetened with sucrose (50 g/l) for 6 months.

Water-Activated Semiquinone Formation and Carboxylic Acid Dissociation in Melanin Revealed by Infrared Spectroscopy.

Eumelanin is a widespread biomacromolecule pigment in the biosphere and has been widely investigated for numerous bioelectronics and energetic applications. Many of these applications depend on eumelanin's ability to conduct proton current at various levels of hydration. The origin of this behavior is connected to a comproportionation reaction between oxidized and reduced monomer moieties and water.

[Antioxidant effect of cortexin, cerebrolysin and actovegin in rats with chronic cerebrovascular insufficiency].

Objective: To compare the antioxidant effects of cortexin, cerebrolysin and actovegin in rats with chronic brain ischemia.

Material And Methods: Chronic brain ischemia was modeled in male rats by 50% stenosis of the common carotid arteries. Forty days after surgery, the animals received 2 ten-day courses of therapy, separated by a break of 10 days.

Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats.

This study was the first to compare the neuroprotective activity of Cerebrolysin®, Actovegin® and Cortexin® in rodent models of acute and chronic brain ischemia. The neuroprotective action was evaluated in animals with acute (middle cerebral artery occlusion) or chronic (common carotid artery stenosis) brain ischemia models in male rats. Cortexin® (1 or 3 mg/kg/day), Cerebrolysin® (538 or 1614 mg/kg/day) and Actovegin® (200 mg/kg/day) were administered for 10 days.

Klotho Protein and Cardio-Vascular System.

Klotho protein affects a number of metabolic pathways essential for pathogenesis of cardio-vascular diseases and their prevention. It inhibits lipid peroxidation and inflammation, as well as prevents endothelial injury and calcification of blood vessels. Klotho decreases rigidity of blood vessels and suppresses development of the heart fibrosis.

Effect of RGPU-260, a Novel GABA Derivative, on Functional Reserves of Rat Heart after Chronic Alcohol Intoxication.

The effect of a new derivative of GABA, the compound RGPU-260, on the heart contractility of rats exposed to chronic alcohol intoxication (10% ethanol solution for 24 weeks) was studied. In comparison with intact rats, the alcoholized ones were characterized with smaller increments in the rates of myocardial contraction (+dP/dt) and relaxation (-dP/dt), left ventricular pressure, and maximum intensity of functioning of structures during the load tests (volume load/preload, stimulation of the cardiac adrenergic receptors, and occlusion of the ascending aorta/afterload) attesting to degraded cardiac contractility function. In rats treated with RGPU-260 (daily, 25 mg/kg intragastrically during 14 days), these parameters were higher in comparison with control values indicating a positive action of the examined agent on inotropic function of the heart.

Cardioprotective effects of a new glutamic acid derivative in chronic alcohol intoxication.

Alcohol abuse is a risk factor for heart damage and deterioration of its inotropic function. Currently, there is no pathogenetic pharmacological treatment for alcohol-induced myocardial injury. Therefore, the study of drugs with cardioprotective action is of current interest.

Peculiarities of the Expression of Inducible NO Synthase in Rat Dentate Gyrus in Depression Modeling.

Mild stress exposure contributes to the development of cognitive and emotional deficits, is considered as a model of depressive state, and is characterized by enhanced NO production. In albino mature (12-month-old) male rats, the depressive state was simulated by daily 30-min exposure to stressful stimuli (vibration, loud sound, and strobe light) over 7 days in a special chamber. On paraffin frontal sections of the brain stained with antibodies against inducible NO synthase (iNOS), the expression and distribution pattern of immunoreactive material were evaluated in various layers of the dentate gyrus under normal conditions and after depression modeling.

[Comparative study of protective effects of Cortexin, Cerebrolysin and Actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia].

Objective: To compare the effects of cortexin, cerebrolysin and actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia.

Material And Methods: The study was conducted using male rats with chronic brain ischemia caused by stenosis of the common carotid arteries by 50%. Animals received cortexin (0,3; 1 or 3 mg/kg), cerebrolysin (0,8; 2,5 or 7,5 ml/kg) and actovegin (5 ml/kg) in two 10-day courses with 10 days of treatment break.

Correction of Alcohol-Induced Damage to Mitochondria in Cardiac and Cerebral Cells by Derivatives of Neuroactive Amino Acids.

We studied LPO intensity and respiration of mitochondria in brain and heart cells of rats receiving 5% ethanol for 20 weeks and treated with derivatives of neuroactive amino acids. Chronic semicompulsory alcohol intoxication increased the concentration of LPO products in cardiac and cerebral mitochondria by 46 and 45% (diene conjugates), by 97 and 8% (diketones), and by 28 and 81% (malondialdehyde), respectively, reduced activity of antioxidant enzymes in cardiac and cerebral mitochondria by 24 and 45% (glutathione peroxidase) and by 22 and 26% (superoxide dismutase), respectively, and uncoupled the process of respiration and ATP synthesis, which manifested in a decrease in respiratory control (V/V ratio according to Chance). Glutamic acid derivative Neuroglutam (26 mg/kg) and GABA derivative succicard (44 mg/kg) administered intraperitoneally daily for 28 days after termination of alcoholization decreased the levels of primary and secondary LPO products, up-regulated activity of antioxidant enzymes in mitochondria of the heart and brain, and moderated the mitochondrial dysfunction.

Effects of Gaba Derivatives on Anxious and Compulsive Behavior in Offspring of Rats with Experimental Preeclampsia.

We studied the effects of GABA derivatives on anxious and compulsive behavior of progeny of rats with experimental preeclampsia provoked by replacement of drinking water for 1.8% NaCl solution from the first day of pregnancy to delivery. In comparison with progeny of health rats, the offspring of dams with complicated pregnancy demonstrated high level of anxiety and the development of obsessive-compulsive disorder both at the early (40 and 70 days) and late (6 and 12 months) stages of ontogeny.

[Age-specific changes in the functional indices of rats' cardiac mitochondria in chronic alcohol intoxication.].

The effect of chromic continuous consumption of 5 and 10% ethyl alcohol over 6 months on the respiratory function and oxidant/antioxidant status of rats' cardiac mitochondria of different gender and age has been studied. A decrease in oxygen consumption rate by cardiomyocyte mitochondria in the metabolic conditions V2, V3, V4 according to Chance involving activation of respiratory chain complexes I, I+II and II in elderly (24-month old) animals as compared to young (11-month old) animals. As the rats were ageing, the concentration of lipid peroxidation (LPO) products (malondialdehyde) was increasing, while the activity of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) was decreasing in cardiomyocyte mitochondria.

Synthesis and biological evaluation of 3-substituted 2-oxindole derivatives as new glycogen synthase kinase 3β inhibitors.

Glycogen synthase kinase 3β (GSK-3β) is a widely investigated molecular target for numerous diseases including Alzheimer's disease, cancer, and diabetes mellitus. Inhibition of GSK-3β activity has become an attractive approach for treatment of diabetes and cancer. We report the discovery of novel GSK-3β inhibitors of 3-arylidene-2-oxindole scaffold with promising activity.

Composition and cardioprotective effects of Primula veris L. solid herbal extract in experimental chronic heart failure.

Background: High interest in chronic heart failure (CHF) is accounted for by its high incidence, poor prognosis, growing number of hospital admissions due to the heart failure relapse, and inadequate treatment. These facts necessitate a search for new pharmacological agents for the CHF correction. Herbal medicinal products appear to be very promising as they have a noticeable therapeutic effect and tend to be more harmless in comparison to the most of synthesized medications.

Chemistry and Hypoglycemic Activity of GPR119 Agonist ZB-16.

This article is to highlight the chemical properties and primary pharmacology of novel GPR119 agonist ZB-16 and its analogs, which were rejected during the screening. Experiments were performed (specific activity, metabolism and cell toxicity) and (hypoglycemic activity and pharmacokinetics). ZB-16 exhibits nanomolar activity (EC50 = 7.

[Influence of the dense extract from herb of Primula veris L. On the oxidative stress development and the functional state of the cardiomyocytes mitochondria of rats with experimental chronic heart failure].

Experimental chronic heart failure (CHF), caused by administration of L-isoproterenol (2.5 mg/kg twice a day intraperitoneally for 21 days), promotes uncoupling of respiration and oxidative phosphorylation. The rate of mitochondrial oxygen consumption in the metabolic state V3 by Chance in animals with CHF decreased by 53.

Expression of Beclin-1 and LAMP-2 in Rat Hippocampus under Conditions of Simulated Gravity Overload in the Caudocranial Vector.

Structural changes in the rat hippocampus in response to chronic cerebrovascular disorders induced by gravity exposure in the caudocranial vector were studied. Qualitative and quantitative morphological analysis detected significant cytoarchitectonic changes in the pyramidal layer: spongiosis, manifest pericellular and perivascular edema, and a drastic increase in the counts of pyramidal neurons with signs of impairment in all hippocampal zones. The density of perikarya in the pyramidal layer decreased.

Evaluation of DNA Damage in Experimental Preeclampsia by Comet Assay.

Experimental preeclampsia induced by substitution of drinking water with 1.8% NaCl during pregnancy was associated with an increase in the level of DNA damage in fetal brain and placenta measured by DNA comet assay by 35.7 and 27.