Interplay between conformational flexibility, intermolecular H-bonding and 3d-metal cation extraction ability in a series of thiacalix[4]arene lower rim disubstituted Schiff base derivatives.

The rational design of organic ligands with the aim to control their binding abilities towards different metal ions can be considered as one of the key concepts in supramolecular coordination chemistry. Regarding the macrocyclic compounds of thiacalix[4]arene family, this can be achieved the targeted modulation of macrocyclic platform rigidity as well as the proper choice of appended binding sites. Four macrocyclic salen-type ligands based on lower rim disubstituted thiacalix[4]arene derivatives, adopted in a cone conformation, bearing highly coordinating iminophenolic or catecholic groups and two -CH- moieties as spacers but presenting different abilities to form H-bonds, were chosen to elucidate the interplay between the conformational flexibility of the macrocyclic ligands, propensity to participate in the intermolecular H-bonding and the extraction ability of 3d-metal cations.

(2-Hydroxy-3-Methoxybenzylidene)thiazolo[3,2-]pyrimidines: Synthesis, Self-Assembly in the Crystalline Phase and Cytotoxic Activity.

A series of new 2-hydroxy-3-methoxybenzylidenethiazolo[3,2-]pyrimidines with different aryl substituents at the 5 position are synthesized and characterized by H/ C NMR and IR-spectroscopy and mass-spectrometry, as well as single crystal X-ray diffraction (SCXRD). It was demonstrated that the type of hydrogen bonding can play a key role in the chiral discrimination of these compounds in the crystalline phase. The hydrogen bond of the O-H.

Synthesis, Self-Assembly in Crystalline Phase and Anti-Tumor Activity of 2-(2-/4-Hydroxybenzylidene)thiazolo[3,2-]pyrimidines.

A series of new thiazolo[3,2-]pyrimidines different by aryl substituents in 2 and 5 positions are synthesized and characterized in solution as well as in the crystalline phase using H and C NMR-, IR-spectroscopies, mass-spectrometry methods, and single crystal X-ray diffraction (SCXRD). The SCXRD study revealed the role of intermolecular H-bonding in the formation of supramolecular architectures (racemic monomers, centrosymmetric racematic dimers, or homochiral 1D chains) of obtained thiazolo[3,2-]pyrimidines derivatives depending on solvents (aprotic DMSO or protic EtOH) used upon the crystallization process. Moreover, the in vitro study of cytotoxicity toward different tumor cells showed their high or moderate efficiency with moderate cytotoxicity against normal liver cells which allows to consider the obtained thiazolo[3,2-]pyrimidine derivatives as promising candidates for application as antitumor agents.

Influence of 10-(6-plastoquinonyl) decyltriphenylphosphonium on free-radical homeostasis in the heart and blood serum of rats with streptozotocin-induced hyperglycemia.

Background: It is known that under conditions of tissue tolerance to insulin, observed during type 2 diabetes mellitus (DM2), there is an increased production of reactive oxygen species. Moreover, the free radicals can initiate lipid peroxidation (LPO) in lipoprotein particles. The concentration of LPO products can influence the state of insulin receptors, repressing their hormone connection activity, which is expressed as a reduction of the glucose consumption by cells.

Efficacy and safety of blonanserin transdermal patch in patients with schizophrenia: A 6-week randomized, double-blind, placebo-controlled, multicenter study.

Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia.

Methods: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches.

Discovery of vascular Rho kinase (ROCK) inhibitory peptides.

Unlabelled: Rho-activated kinases (ROCKs) regulate many cellular functions such as proliferation, migration, and smooth muscle contractility, but they are also associated with pathogenesis of many human diseases such as heart failure and hypertension. We used phage display libraries to identify inhibitory polypeptides that bind to the ROCK1 catalytic domain, but do not compete with the ATP-binding pocket, by screening in the presence of high ATP concentrations (1 mM). Peptide7, a promising ROCK inhibitory peptide for both ROCK isoforms, measured at 1.

Validation of the Russian Version of the Positive and Negative Syndrome Scale (PANSS-Ru) and Normative Data.

: The Positive and Negative Syndrome Scale (PANSS) is widely used to assess psychopathology. The Russian version (PANSSRu) has not been validated, and normative data for the Russian-speaking population currently do not exist. The aims of this study were to 1) complete linguistic validation for the PANSSRu, 2) perform psychometric validation of the Russian translation, and 3) present norms for the Russian and Belarusian population.

Identification of 5-hydroxytryptamine receptor gene polymorphisms modulating hyperprolactinaemia in antipsychotic drug-treated patients with schizophrenia.

Objectives: Hyperprolactinaemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 subtype receptors in the pituitary gland. Although dopamine is considered the primary factor inhibiting prolactin release, the activity of prolactin-producing lactotrophs is also regulated by the secretagogues thyrotrophin releasing hormone, vasoactive intestinal polypeptide and serotonin (5-hydroxytryptamine; 5-HT).

Methods: We describe the association between HPRL and a set of 29 SNPs from 5-HT receptor genes HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6 in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) who were treated with classical and/or atypical antipsychotic drugs.

[The effect of 3,5-dicarbomethoxyphenylbiguanide on the activity of antioxidant enzymes].

The effect of 3,5-dicarbomethoxyphenylbiguanide, which was selected with the Prediction of Activity Spectra of Substances (PASS) computer program, on the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase in the heart and the blood serum of rats with experimental rheumatoid arthritis was investigated. The studied parameters changed towards control values when the tested compound was injected in animals with the pathology. These results can be explained by the cardioprotective and antioxidant activity of the compound.

Effect of SkQ1 on Activity of the Glutathione System and NADPH-Generating Enzymes in an Experimental Model of Hyperglycemia.

We studied the effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on the antioxidant activity of the glutathione system and NADPH-generating enzymes in liver and blood serum of rats with hyperglycemia induced by protamine sulfate. It was found that intraperitoneal injection of SkQ1 prevented both decrease in reduced glutathione level and increase in activity of glutathione system enzymes--glutathione peroxidase, glutathione reductase, and glutathione transferase. Activity of NADPH-generating enzymes--glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase--was also attenuated by SkQ1.

Influence of 10-(6'-Plastoquinonyl)decyltriphenylphosphonium (SkQ1) on Oxidative Status in Rats with Protamine Sulfate-Induced Hyperglycemia.

An influence of 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on oxidative status and activity of some antioxidant enzymes in the liver and blood serum from rats was examined during experimental hyperglycemia developed after injecting protamine sulfate. It was found that SkQ1 lowered glycemic level in rats treated with protamine sulfate. Moreover, it was also accompanied by restoration of the normal range of biochemiluminescence parameters indicating the rate of ongoing free radical processes, magnitude of primary products of lipid peroxidation such as diene conjugates, activity of aconitate hydratase, and level of citrate in rat liver and blood.

[Effect of melaxen on free radical processes intensity and some antioxidant enzymes activity in rats liver and blood serum under type 2 diabetes mellitus].

The effect of melaxen on free radical processes and activity of superoxide dismutase and catalase in rats with type 2 diabetes mellitus (T2DM) has been investigated. It was established that melaxen administration to diabetic rats caused a decrease of the intensity of free radical processes as evidenced a decrease of the lipid peroxidation primary products content and biochemiluminescence parameters. The activity of the antioxidant enzymes changed towards normal values.

[Intensity of apoptotic processes, aconitate hydratase activity and citrate level in patients with type 2 diabetes mellitus complicated steatohepatitis under application of epifamin at basic therapy].

DNA fragmentation, caspase-1 and caspase-3, aconitate hydratase (AH) activities, and citrate content have been investigated in the blood of patients with type 2 diabetes mellitus complicated by steatohepatitis. These indicators of apoptotic processes intensity and oxidative stress development were estimated after basic treatment and a combined therapy including epifamin. Before treatment DNA fragmentation blood leukocytes, decrease of AH activity and increase of caspases activities in the serum of patients were detected.

Effects of Melatonin-Aided Therapy on the Glutathione Antioxidant System Activity and Liver Protection.

Acute hepatitis results from oxidative stress triggered by hepatotoxic drugs causing liver injury and the activation of caspases cascade. The glutathione antioxidant system protects against reactive oxygen species and mitigates development of these processes. The effectiveness of silymarin, a polyphenolic flavonoid, essenthiale, composed of phosphatidyl choline, and melaxen, a melatonin-correcting drug, as hepatoprotectors has been investigated.

[Effect of melaxen and valdoxan on free radical processes intensity, aconitate hydratase activity and citrate content in rats tissues under hyperthyroidism].

The influence of melaxen and valdoxan on the biochemiluminescence parameters, aconitate hydratase activity and citrate level in rats heart and liver during development of experimental hyperthyroidism has been investigated. Administration of these substances promoted a decrease of biochemiluminescence parameters, which had been increased in tissues of rats in response to the development of oxidative stress under hyperthyroidism. Aconitate hydratase activity and citrate concentration in rats liver and heart, growing at pathological conditions, changed towards control value after administration of the drugs correcting melatonin level.

The effect of melaxen on the activity of caspases and the glutathione antioxidant system in toxic liver injury.

A comparative study of the activity of caspase-1 and caspase-3, the glutathione antioxidant system and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase) and a study of DNA fragmentation in the blood serum of patients with chronic alcoholic hepatitis during basic treatment and combination therapy including melaxen have been carried out. It was found that the blood serum level of reduced glutathione, which decreases in pathology, increased more significantly in patients receiving melaxen as compared to the group of patients receiving the standard treatment. More significant changes in the activity of caspase-1 and caspase-3, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase toward the control values were observed during the combination therapy.

Activity of the glutathione antioxidant system and NADPH-generating enzymes in blood serum of rats with type 2 diabetes mellitus after administration of melatonin-correcting drugs.

We studied the effects of epifamin and melaxen on serum content of reduced glutathione and activities of glutathione peroxidase, glutathione reductase, and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase) in rats with type 2 diabetes mellitus. The concentration of reduced glutathione was decreased in rats with this disease (by 1.8 times), but increased after treatment with epifamin and melaxen (by 1.

[Effect of melatonin on antioxidant state under type ii diabetes at rat].

The effect of melatonin on the intensity of free radical processes and activities of superoxide dismutase (SOD, EC 1.15.1.

Intensity of Free Radical Processes in Rat Liver under Type 2 Diabetes and Introduction of Epifamin.

The effect of epifamin on free radical processes, the activity of caspase-1 and -3, aconitate hydratase and citrate content in rat's liver at experimentally induced type 2 diabetes mellitus (T2DM) was studied. The action of epifamin at T2DM leads to a decrease in biochemiluminescence parameters, characterizing the intensity of free radical processes, and changes in aconitase activity and citrate level towards the control. Activities of caspase-1 and caspase-3 in the tissue decreased by a factor of 2.

Expression of Glutathione Peroxidase and Glutathione Reductase and Level of Free Radical Processes under Toxic Hepatitis in Rats.

Correlation between intensity of free radical processes estimated by biochemiluminesce parameters, content of lipoperoxidation products, and changes of glutathione peroxidase (GP, EC 1.11.1.

Peptide inhibitors disrupt the serotonin 5-HT2C receptor interaction with phosphatase and tensin homolog to allosterically modulate cellular signaling and behavior.

Serotonin (5-hydroxytryptamine; 5-HT) signaling through the 5-HT(2C) receptor (5-HT(2C)R) is essential in normal physiology, whereas aberrant 5-HT(2C)R function is thought to contribute to the pathogenesis of multiple neural disorders. The 5-HT(2C)R interacts with specific protein partners, but the impact of such interactions on 5-HT(2C)R function is poorly understood. Here, we report convergent cellular and behavioral data that the interaction between the 5-HT(2C)R and protein phosphatase and tensin homolog (PTEN) serves as a regulatory mechanism to control 5-HT(2C)R-mediated biology but not that of the closely homologous 5-HT(2A)R.

Effect of N-[Imino(4-morpholyl)methyl]guanidine on the oxidative status in rats with toxic hepatitis.

The hepatoprotective and antioxidant properties of a synthetic biguanide N-[imino(4-morpholyl)methyl]guanidine (IMMG) were prognosticated by the method of computer prediction. Administration of IMMG was accompanied by a decrease in serum transaminase activity in rats with toxic hepatitis, which reflects inhibition of hepatocyte cytolysis. IMMG treatment was followed by a decrease in biochemiluminescence parameters reflecting the intensity of free radical oxidation.

[Catalytic properties of glutathione reductase from rats liver at norm and toxic hepatitis].

Homogeneous preparations of liver glutathione reductase (GR, EC 1.6.4.

Preparation of a library of unsymmetrical ureas based on 8-azabicyclo[3.2.1]octane scaffold.

This paper reports the preparation of a library of unsymmetrical ureas based on 8-azabicyclo[3.2.1]octane scaffold.

Substrate specificity and screening of the integral membrane protease Pla.

This paper reports a study to find small peptide substrates for the important virulence factor of Yersinia pestis, plasminogen activator, Pla. The method used to find small substrates for this protease is reported along with studies examining the ability of these peptides to inhibit activity of the enzyme. Through the use of parallel synthesis and positional scanning, small tripeptides were identified that are viable substrates for the protease.