ANTIBACTERIAL AND CENTRAL NERVOUS SYSTEM ACTIVITY OF (4,5-DIARYL-4H-1,2,4-TRIAZOL-3-YL)METHACRYLIC ACID DERIVATIVES.

The series of 1,2,4-triazole derivatives containing methacrylic acid moiety were synthesized in reaction of N3-substituted amidrazones with itaconic anhydride. Preliminary calculated bioavailability parameters of obtained compounds suggested good penetration via cell membranes and their good absorption after oral intake. Antimicrobial evaluation in vitio showed diverse activity of obtained triazoles mainly on Gram-positive bacterial strains.

SYNTHESIS, STRUCTURE AND PHARMACOLOGICAL EVALUATION OF 1-(1H-PYRROL-1-YLMETHYL)-4-AZATRICYCLO[5.2.1.0(2,6)] DEC-8-ENE-3,5-DIONE.

A set of arylpiperazine derivatives with imide fragments, 1-(1H-pyrrol-1-ylmethyl)-10-oxa-4-azatricyclo[5.2.1.

Impact of combined treatment with rosuvastatin and antidepressants on liver and kidney function in rats.

Depression is among the most prevalent and life-threatening forms of mental illness, and is also a risk factor for cardiovascular disorders, diabetes and metabolic syndrome. Elderly patients commonly receive statins for the prevention of cardiovascular diseases, and antidepressant drugs for the treatment of depression. It should be noted that long-term polypharmacotherapy may lead to potential drug interactions and disorders of the organs.

Preliminary Pharmacological Screening of Some Thiosemicarbazide, s-triazole, and Thiadiazole Derivatives.

Two thiosemicarbazide derivatives 1 and 2, three 2-amino-1,3,4-thiadiazole derivatives 3-5, and three N1- substituted-4-methyl-1,2,4-triazole-5-thione derivatives 6-8 were synthesized and evaluated for their central nervous system effects using rodent behavioral models. With the exception of 6, all compounds were devoid of neurotoxicity and they did not affect the body temperature of mice. New lead structures 1-4 with potential analgesic activity were identified.

Estimation of oxidative stress parameters in rats after simultaneous administration of rosuvastatin with antidepressants.

Background: Patients commonly receive statin drugs for the primary or secondary prevention of cardiovascular events and also commonly receive antidepressant drugs for the treatment of depression. A many-year polypharmacotherapy can lead to increased side effects of these drugs. It may lead to an oxidation-reduction imbalance and the growth of a generation of reactive oxygen species (ROS) which may induce cellular dysfunctions.

EVALUATION OF SELECTED BIOCHEMICAL PARAMETERS OF OXIDATIVE STRESS IN RATS PRETREATED WITH ROSUVASTATIN AND FLUOXETINE.

The aim of this study was to assess the effect of a combined 14-day treatment with rosuvastatin (10 mg/kg) and fluoxetine (10 mg/kg) on selected biochemical parameters of oxidative stress in the blood of rats. The activity of glutathione peroxidase (GPX), glutathione reductase (GR) and the total antioxidant status (TAS) were determined. A combined 14-day treatment with rosuvastatin and fluoxetine significantly increases glutathione peroxidase and glutathione reductase activity and decreases the level of TAS.

Preliminary studies evaluating cytotoxic effect of combined treatment with methotrexate and simvastatin on green monkey kidney cells.

Patients, affected by neoplastic disease, take usually other drugs and this may lead to a number of often rather unpredictable interactions. The statins are among the most commonly prescribed drugs in medicine but have also adverse side effects and come into interactions with other drugs. The aim of this study was to investigate the cytotoxic effect of methotrexate (5.

The influence of lead on the biomechanical properties of bone tissue in rats.

Introduction And Objective: Environmental lead (Pb) is a serious public health problem. At high levels, Pb is devastating to almost all organs. On the other hand, it is difficult to determine a safe level of exposure to Pb.

The problem of osteoporosis in epileptic patients taking antiepileptic drugs.

Introduction: Epilepsy is a common neurological disorder associated with recurrent seizures. Therapy with antiepileptic drugs (AEDs) helps achieve seizure remission in approximately 70% of epileptic patients. Treatment with AEDs is frequently lifelong and there are reports suggesting its negative influence on bone health.

Influence of combined therapy with rosuvastatin and amitriptyline on the oxidation-reduction status in rats.

The aim of the present study was to assess the impact of combined therapy with rosuvastatin (10 mg/kg) and amitriptyline (10 mg/kg) on oxidation-reduction status in the blood of rats. After 2-week application of drugs alone or their combination, the activity of glutathione peroxidase (GPX), glutathione reductase (GR) and total antioxidant status (TAS) were determined. It was noticed that combined therapy with rosuvastatin and amitriptyline significantly increased the activity of GPX in comparison to the group receiving only rosuvastatin and decreased the activity of GR in comparison to groups receiving only rosuvastatin or amitriptyline.

Biological activity of novel N-substituted amides of endo-3-(3-methylthio-1,2,4-triazol-5-yl)bicyclo[2.2.1]hept-5-ene-2-carboxylic acid and N-substituted amides of 1-(5-methylthio-1,2,4-triazol-3-yl)cyclohexane-2-carboxylic acids.

N-Substituted amides of endo-3-(3-methylthio-1,2,4-triazol-5-yl)bicyclo[2.2.1]hept-5-ene-2-carboxylic acid and 1-(5-methylthio-1,2,4-triazol-3-yl)cyclohexane-2-carboxylic acid were prepared by the condensation reaction of endo-S-methyl-N1-(bicyclo[2.

Pharmacological study on some new 3-[(1-methylpyrrol-2-yl)-methyl]-4-substituted 4,5-dihydro-1H-1,2,4-triazol-5-ones.

3-[(1-Methylpyrrol-2-yl)methyl]-4-substituted 4,5-dihydro-1H-1,2,4-triazol-5-ones were obtained by the cyclization reaction of 1-[(1-methylpyrrol-2-yl)acetyl]-4-substituted semicarbazides in alkaline medium. The effects of the synthesized compounds of the central nervous system of mice were studied.

Synthesis of amides of 2,4-dioxothiazolidin-5-yl acetic acid with 1,2,4-triazole substituents.

In the reaction of (2,4-dioxothiazolidin-5-yl)acetyl chloride with 1,2,4-triazole, 4-phenyl-1,2,4-triazolin-5-one and 4-phenyl-1,2,4-triazolin-5-thione, the new corresponding amides (2-4) were obtained. For compounds 2 and 4 effects on central nervous system (CNS) of mice were studied.

Cyclization of thiosemicarbazide derivatives of 5-arylidene-2,4-dioxothiazolidine-3-acetic acids to 1,3,4-thiadiazoles and their pharmacological properties.

By the reaction of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetyl chlorides with 4-phenylthiosemicarbazide, acylthiosemicarbazide derivatives 4-6 were obtained. The cyclization of 4-6 in acid medium led to 1,3,4-thiadiazole derivatives 7-9. The structure of the compounds was confirmed by elemental analysis and IR, H NMR, 13C NMR and MS spectra.

Synthesis and biological activity of new derivatives of 3-phenoxymethyl-4-R-D2-1,2,4-triazoline-5-thione.

New derivatives of 1,2,4-triazoline-5-thione system were obtained. The effects of both these compounds AP-I (3-phenoxymethyl-4-phenyl-D2-1,2,4-triazoline-5-thione) and AP-II (3-phenoxymethyl-4-ethyl-D2-1,2,4-triazoline-5-thione) on the central nervous system (CNS) of mice were studied.

Synthesis and some pharmacological properties of 3-(piperidin-4-yl)-4-substituted-D2-1,2,4-triazoline-5-thione derivatives.

Synthesis of 3-(piperidin-4-yl)-4-substituted-D-2-1,2,4-triazoline-5-thione derivatives, AS-1-AS-4 is described. Results of a preliminary pharmacological screening of two compounds AS-1 and AS-3 are presented.

Synthesis and biological activity of new derivatives of 3-(3,4-diaryl-1,2,4-triazole-5-yl)propenoic acid.

New 3-(3,4-diaryl-1,2,4-triazole-5-yl)propenoic acid derivatives (8-14) were synthesized by condensation of N(3)-substituted amidrazones (1-7) with maleic anhydride. Molecular structure of obtained compounds was confirmed by an elemental analysis, IR and (1)H NMR spectra, and the X-ray crystallography for compound 11. The influence of the compound 9 on the central nervous system (CNS) of mice in some behavioural test was examined.

[Activity of catalase after administration of some ADH and MEOS inhibitors: in vitro investigation in rat liver homogenates].

In the first pass methanol biotransformation three enzymatic systems: alcohol dehydrogenase (ADH), microsomal alcohol oxidising system (MEOS) linked with cytochrome P-450 and catalase are involved. Because of the toxicity of methanol, which is directly caused by its toxic metabolites, the major task in clinical toxicology is to inhibit each of these enzymes to protect human life. The aim of this investigation was to check the influence of some effective inhibitors of ADH and MEOS: 4-methylpyrazole, cimetidine, EDTA and 1,10-phenantroline on the activity of catalase with methanol as a substrate and the comparison with 3-amino-1,2,4-triasole.

Preliminary evaluation of CNS effects of 6-O-substituted chelidonine derivatives.

Eleven new derivatives of chelidonine I, obtained by functionalization of the alkaloid hydroxyl group, have been tested for CNS activity in mice exhibiting statistically significant effects.

Synthesis and pharmacological properties of sulfur derivatives of indane-1,3-dione.

Synthesis of sulfur derivatives of indane-1,3-dione, VIIb-c, VIIIa-b, IX and X is described. Results of a preliminary pharmacological screening of six compounds [VIIb, VIII, VIIIb, IX, X and XI] are presented.

Synthesis and some pharmacological properties of 3-(4-phenyl-5-oxo-1,2,4-triazolin-1-ylmethyl)-1,2,4-triazolin-5-thione derivatives.

In the reaction of (4-phenyl- or 3,4-diphenyl-5-oxo-1,2,4-triazeolin-1-ylmethyl)-carbohydrazide (IIa, IIb) with isothiocyanates the thiosemicarbazide derivatives [IIIa, b - IXa, b] were obtained. Cyclization of those compounds in the presence of 2% or 10% NaOH led to formation of derivatives with the 1,2,4-triazolin-5-thione system [Xa, b - XV[a, b]. Molecular structure proposed for this group of compounds was confirmed by X-ray structure analysis of Xa and XIVa.