Репозитарій

Abstract. The article examines the problem of ensuring the psychological stability of students during the war.  The level of psychological stability of the student in connection with his visit was analyzed.  A study was conducted using a survey of students of several universities in Ukraine.  The developed questionnaire made it possible to outline that most students feel anxiety and fear.  The influence of the psycho-emotional state during the war on the educational performance of students was determined.  There are ways to reduce the feeling of anxiety, tension, fear and directions of adjustment  of  the  psychological  climate  in  the  context  of  resistance  to  stressful  situations.  The object of this study is the psychological stability of students during university studies and studies under martial law.  The subject of the study is the peculiarities of the formation of psychological stability in students and the means of its formation. The purpose of the study is to determine the psychological  conditions  for  the  formation  of  students'  psychological  stability.    Factors  of stressogenicity and psychological stability of students in war conditions were studied. The  research  revealed  the  psychological  essence  of  stress  resistance  and  psychological resilience. On the basis of the survey, the mental state of students of higher education institutions during  the  war  was  analyzed.  The  methods  of  increasing  the  level  of  psychological  stability  of students  while  studying  during  the  war  are  considered.  Practical  recommendations  on  the formation  of  stress  resistance  and  psychological  stability  of  students  of  higher  education institutions during the war are presented.

Abstract

   Development of an effective and safe antioxidant compound is still challenging in the last few decades. There has been an increasing interest in the role of reactive oxygen species (ROS) in food, drugs, and even living system. Free radical formation is associated with the normal natural metabolism of aerobic cells. They are inevitably exposed to reactive oxygen species formed as oxygen metabolites. Oxidative stress which is largely characterized by reactive oxygen and nitrogen species is implicated in the development of a number of chronic and degenerative diseases such as atherosclerosis, cancer, cirrhosis, diabetes, wound healing and aging. Free radicals are highly reactive and therefore can attack membrane lipids, generating carbon radicals and peroxy radicals, which cause lipid peroxidation. Therefore, scientists in various disciplines have become more interested in naturally-occurring antioxidants as well as in related synthetic derivatives that could provide active components which prevent or reduce the impact of oxidative stress. Іn order to study the effect of various substituents in the molecules on the nature of thepharmacological activity of thiazolo[4,5-b]pyridin-2-ones, a series of new compounds were synthesized based on the previously obtained 5,7-dimethyl-3Hthiazolo[4,5-b]pyridin-2-one. The high electrophilicity of the N3 position in 5,7-dimethyl-3H-thiazolo[4,5-b]pyridin- 2-one allows to use of its functionalization as a convenient method for obtaining various N3-substituted derivatives to expand the range of thiazolo[4,5-b]pyridines. In particular, an NH center with a mobile hydrogen atom at the N3 position in 5,7-dimethyl-3H-thiazolo[4,5-b]pyridin-2-one allows conducting a synthesis based on 3-substituted derivatives. This conversion was carried out through the stage of obtaining potassium salt. Several chloroacetamides were tested as alkylating agents, which allowed to obtain the corresponding 2-(5,7-dimethyl-2-oxo-thiazolo[4,5-b]pyridin-3-yl)-N-aryl-acetamides (1–6). Methods of quantitative elemental analysis, mass spectrometry, and 1H NMR spectroscopy were used to confirm the structure and individuality of the synthesized substances. Interpretation of the spectra revealed that the signals for protons of all structural units were observed in their characteristic ranges.

Mounting research has been performed in the recent decades focusing on natural and low-molecular-weight synthetic antioxidants discovering as key molecules that control oxidative damage and its pathway to disease.

Oxidative stress is a phenomenon resulting from the imbalance between oxidation-reduction processes, in particular, the formation and accumulation reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells and tissues, and the ability of the antioxidant defence system of the organism to eliminate these by-products. Oxidative stress develops under the influence of external or internal factors and leads to oxidative modification of biomolecules, in particular lipids, proteins and DNA [6]. One- and two-electron oxidation-reduction reactions, as an integral part of aerobic metabolism, often lead to free radicals’ in vivo formation. Molecular oxygen reduction processes include the stepwise single electron reduction of O₂ results in such ROS generation as superoxide anion radical (O₂^•-), hydrogen peroxide (H₂O₂) and hydroxyl radical (HO^•). H₂O₂ is produced as a result of two-electron O₂ reduction. Reactive nitrogen species include mainly nitric oxide (NO^•), nitrogen dioxide (NO₂^•) and peroxynitrite (ONOO⁻), as well as non-radicals such as nitrous acid HNO₂ and N₂O₄ (dinitrogen tetroxide).

At lower concentrations ROS/RNS have beneficial effects and indulged in different physiological processes such as redox regulation, mitogenic responses, cellular signaling pathways, and an immune function while at a higher level, these reactive species generate nitrosative and oxidative stress.

In modern research the two main types of antioxidants are distinguished: (1) the primary antioxidants, or free radical scavengers, which are able to break the chain reaction; (2) the secondary, or preventive, antioxidants, for which the action mechanisms may include the deactivation of metals, inhibition of lipid hydroperoxides by interrupting the production of undesirable volatiles, the regeneration of primary antioxidants, and the elimination of singlet oxygen. The methods of the antioxidant capacity determining are commonly classified into two main groups, based on the reaction mechanisms involved in free radicals’ reduction process: (a) hydrogen atom transfer (HAT) reactions; and (b) transfer reactions of a single electron (SET). 

Nowadays the discovery of effective antioxidant agents among low-molecular-weight organic molecules is a recent problem that requires new methodological approaches implementation, while it is also the society relevant task [1]. Both thiazole and pyridine scaffolds are of the highest priority in modern medicinal chemistry [2, 3]. Numerous reports concerning variety biological effects possessed by thiazolopyridine derivatives have been currently published including their discovery as potent antioxidant agents [4].

One of the antioxidant action mechanisms can be exerted through the inhibition enzymes’ activity which are responsible for reactive oxygen species (ROS) producing, thereby reducing oxidative stress. The objective of the precent study was to fulfil molecular docking studies of novel 3H-thiazolo[4,5-b]pyridine-2-one derivatives towards lipoxygenase (LOX) as one of ROS-producing enzymes. LOX-5 is the enzyme that catalyses the oxidation of polyunsaturated fatty acids to form lipid hydroperoxides, which can lead to membrane damage and inflammation.

The objects of the precent research were three series of condensed 3H-thiazolo[4,5-b]pyridine derivatives, synthesized at Danylo Halytsky Lviv National Medical University [5-7]: (a) the 1^st series included N³ substituted derivatives containing phenyl, propanenitrile, propanoic acid and phenylpropanamide moieties as N³-substituents while they comprised hydroxyl group at C⁵ position; (b) the 2^nd series comprised compounds incorporated substituted phenyl diazonium or alkyl substituents at C⁶ position of the core scaffold; (c) the 3^rd series included derivatives incorporated chloroacetate, chlorobenzoate, benzyloxybenzoate, methoxyphenyl acrylate and substituted phenyltriazolecarboxylate moieties as the substituents at C⁵ position of the core scaffold (Fig. 1). The antioxidant activity evaluation of all tested compounds was reported as a spectrophotometric DPPH assay based on the ability of antioxidant drug candidates possess free radical scavenging potency. Compounds of all three series were found to exhibit moderate and low antioxidant effects.

Probing the action mechanism of 3H-thiazolo[4,5-b]pyridin-2-one derivatives as antioxidants was performed through molecular docking studies towards lipoxygenase. Docking studies, filtering and poses grouping according to the Estimated Affinity towards the biotarget were carried out using SeeSar13.1.0 software (BioSolveIT, Sankt Augustin, Germany) [8]. The crystal structures of lipoxygenase were downloaded from Protein Data Bank using the Protein Mode of the software. Two structures of LOX-5 were downloaded: PDB entry 3O8Y - a 2.39 Å resolution structure of LOX-5 without ligands; PDB entry 6N2W – a 2.71 Å resolution structure of LOX-5 with co-crystallized ligand NDGA (Masoprocol, 4-[(2r,3s)-3-[(3,4-dihydroxyphenyl)methyl]-2-methylbutyl]benzene-1,2-diol).