Optimization of the Search for Neuroprotectors among Bioflavonoids.

For the first time, to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies; these include docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin as well as a program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules-quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, and Catechin-3-gallate-according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.

Antihypertensive and cardioprotective effects of new compound 1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril).

Despite the success which was achieved in the treatment of arterial hypertension, the problem remains actual. At the departments of pharmaceutical chemistry and pharmacology of the Zaporozhye State Medical Institute (Ukraine), our research team isolated the compound 1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril) as derivative of 4-amino-1,2,4-triazole. The objectives of this investigation were the study of cardioprotective and antihypertensive activities of this new compound Hypertril and we used the Spontaneously hypertensive rats (SHR) as an experimental model.

SYNTHESIS OF THE NEW 2-(3,4-DIHYDRO-3-OXO-2H-[1,2,4]TRIAZINO[4,3-C]QUINAZOLIN-4-YL) ACETIC ACID DERIVATIVES AND ANALYSIS OF THEIR ANTIOXIDANT ACTIVITY IN NITROSATIVE STRESS MODELS.

Today we know that NO· and ONOO- are clue pathophysiological factors for progression some ischemic diseases of the central nervous system. So investigation of the antioxidants which will be able to decrease NO· and ONOO- toxicity seems to be very of current interest. The six esters and three amides of 2-(3,4-dihydro-3-oxo-2H-[1,2,4]triazino[4,3-c]quinazolin-4-yl)acetic acid were synthesized for this study, and we showed evidence of antioxidant activity of these new original derivatives.

[INFLUENCE OF QUINAPRIL IN COMBINATION WITH ANGIOLINE ON THE CONNECTIVE TISSUE COMPONENTS IN THE RATS SERUM WITH EXPERIMENTAL HYPERTENSION].

One of the most active inhibitors angiotensin-converting enzyme is quinapril that has a high affinity for tissue ACE, improves endothelial vasodilation, has a wide therapeutic range and beneficient influence on heart rate. A new biological active compound with antioxidant action that has endothelioprotective, cardioprotective, antiischemic action is angiolin. In experimental arterial hypertension in the animals blood serum the activity of collagenase, the content of free and protein connecting fractions of hydroxyproline and indicators that reflect the metabolism of glycosaminoglycans have been increased.

The prospects of medical application of metal-based nanoparticles and nanomaterials.

Current studies, dedicated to metallic (gold, silver, iron, and copper) nanomaterials are reviewed in this paper. This metals own unique physical and chemical properties which determine their application. The medical application of metallic nanomaterials includes therapy and prophylaxis of diseases, development of new drugs and improvement of conventional ones, nanodiagnostics.

[Antiradical activity and membranotropic action of cardio- and vasotropic compounds of varying chemical nature].

Antiradical activity and ability to interaction with phosphatidylcholine bilayer of the physiological active compounds (PhAC), concerning the classes of phenylalkilamines (dobutamine, verapamil), dihydro pyridines (BAY-K-4688, nifedipine), analogues of crown ether (carbicyle, diol) was studied. By means of the method of microcalorimetry and spectrophotometry it was shown the complexing ability PhAC with the phospholipid bilayer of the model membrane. It was stated the simbasity in the changes of the thermal effect of the compounds with the negative inotropic activity during its reaction with phosphatidylcholine bilayer and antiradical activity.

[The effect of sodium salicylate and phenobarbital on the anti-arrhythmia properties of novocainamide and acetylnovocainamide].

CaCl2 and aconitic models of arrhythmias were reproduced in experiments with rats. Sodium salicylate was found to decrease the preventive effect of ecetylnovocainamidum and increased the effect of novocainamidum on ECG changes. Sodium salicylate diminished the preventive effect of acetyl-novocainamidum by elevating myocardial Na+ concentrations, favoured the decrease in myocardial K+ levels, eliminated the preventive effects of novocainamide and acetylnovocainamide by altering myocardial energy metabolism in CaCl2-induced arrhythmia and improved the preventive effect of acetyl-novocainamide on these parameters in aconitic arrhythmia.

[Nuclear magnetic resonance in pharmacology].

The NMR spectroscopy has advantages over other techniques in studying the structure, kinetics and thermodynamics of rapid processes, complex formation and metabolism reactions in the solution. NMR is used for investigating the structure of biologically active substances and drugs, the mechanism of their action as it permits the establishment of chemical shifts of single nuclei in the molecule, the constants of spin-spin interaction, the time of relaxation.

[Structural effects in the sarcolemma of the cardiomyocytes under the action of modulators of the polyphosphoinositide system].

The influence of activators (Ca(2+)-channels stimulator BAY K 8644 and phospholipase C stimulator fMLP) and inhibitors (Ca(2+)-channels blocker verapamil and alpha 1-adrenoceptors blocker prazosin) of the polyphosphoinositide system on cardiomyocytes sarcolemma, was studied. The structural effects of the PPI modifiers seem to be one of the mechanisms of the PPI physiological activity at the membrane level.

[The effect of metabolic agents on the antiarrhythmic activity of novocainamide and acetylnovocainamide].

The effects of potassium malate and sodium succinate on the antiarrhythmic activity of novocainamide and acetylnovocainamide during modelling of chlor-calcium-induced arrhythmia as well as in disorders of cardiac rhythm during modelling of pituitrin-isadrine-induced myocardial infarction were studied. The metabolic agents were found to increase the effectiveness of acetylnovocainamide and the toxicity of novocainamide. To interpret the specific features of the mechanism of the anti-arrhythmic action of the compounds there was studied their ability to form complexes with components of biomembranes and ions of biometals.

[Fractionation of low density lipoproteins in NaBr density gradient].

The method of atherogenic class lipoproteins fractionation by equilibrium zonal centrifugation in SW 41 Ti rotor (density range 1,006-1,063 g/ml) was proposed. Hydrated densities, flotation coefficients and mean diameters of LDL particles from different subfractions were estimated.

[Atherogenic dyslipidemia in adolescents: its relation to ischemic heart disease in their fathers and the possibility of its prognosis].

Comparison of a group of adolescents aged 11-16 years whose fathers had angiographically documented coronary atherosclerosis in youth with those matched by sex and age whose parents were clinically healthy yielded the following discriminant function (DF) involving lipid and apoprotein indices of the plasma lipid system: DF = [apo B] X 0.03-[HDL cholesterol] X 0.04-0.

[Physico-chemical and functional characteristics of a subfraction of low-density lipoproteins isolated by ion-exchange column chromatography].

Fractionation of human blood plasma low density lipoproteins (LDL) was performed by ion-exchange chromatography, using a linear NaCl gradient. It was shown that the binding of LDL subfractions eluted with a low ionic strength buffer (i.e.

[Inotropic effect of strophanthin in combination with calcium on the heart muscle].

The effect of strophanthine-g and its combination with different concentrations of calcium in Tyrode solution was studied in guinea-pig auriculi atrii contracting under the effect of isometric electric stimulation. Addition to Tyrode solution of strophanthine-g combined with calcium promoted the reduction of the positive inotropic effect of the former substance. During perfusion of the muscles with Tyrode solutions containing no calcium, the maintenance of the contractile function of the muscles is secured adequately enough by addition of strophanthine-g combined with low concentrations of calcium.

[Pharmacological aspects of digoxin complex formation with calcium and magnesium cations].

NMR spectroscopy was used to establish the formation of digoxin and digitoxin complexes with calcium ions. Microcolorimetric titration demonstrated the formation of two types of digoxin complexes with magnesium at a ratio of 1:1 and 1:2. It was noticed in rat experiments that digoxin (2.

[K-strophanthin-beta complexing with calcium, magnesium and dysprosium ions].

Nuclear magnetic resonance, microcalorimetry and the use of the ion-selecting electrode evidenced that k-strophanthine-beta forms complexes with the calcium, magnesium and disprosium ions. Changes in the position of the k-strophanthine-beta carbohydrate parts and aglycones signals bear witness to their participation in the complexing.

[Action of isolanide in acute cardiac insufficiency in rats].

Acute teste staged on rats showed low doses of the cardiac glycoside isolanide to bring down the level of total lipids, cholesterol and beta-lipoproteins, without causing any changes in the content of NAD, adenyl nucleotides, non-esterified fatty acids (NEFA) and of phospholipids in themyocardium. Large doses of the drug uniformly reduce the content of all the co-enzymes fractions, the amount of ARP, ADP, cholesterol, beta-lipoproteins and the raise the level of total lipids, phospholipids and NEFA. In cases of acute cardiac insufficiency the drug produces a normalizing action on the co-enzymes and adenyl nucleotides content and reduces that of beta-lipoproteins and cholesterol.