In this study, we examined five previously synthesized compounds and checked their binding affinity towards the SARS-CoV-2 main protease (M pro ) by molecular docking study, and compared the data with three FDA approved drugs, i.e., Remdesivir, Ivermectine and Hydroxychlorochine. In addition, we have investigated the docking study against the main protease of SARS-CoV-2 (M pro ) by using Autodock 4.2 software package. The results suggested that the investigated compounds have property to bind the active position of the protein as reported in approved drugs. Hence, further experimental studies are required. The formation of intermolecular interactions, negative values of scoring functions, free binding energy and the calculated binding constants confirmed that the studied compounds have significant affinity for the specified biotarget. These studied compounds were passed the drug-likeness criteria as suggested by calculating ADME data by SwissADME server. Moreover, the ADMET properties suggested that the investigated compounds to be orally active compounds in human. Furthermore, density functional computations (DFT) were executed by applying GAUSSIAN 09 suit program. In addition, Quantitative Structure-Activity Relationship (QSAR) was studied by applying HyperChem Professional 8.0.3 program.
A targeted search for potential drugs of neurotropic action involves the choice of a basic "pharmacophore", which is advisable to carry out on the basis of the achieved principle among the classes of chemical compounds where active pharmaceutical substances with high targeted activity have already been identified. Therefore, the pyrrolidine core, which is the basic fragment of nootropics of the racetam group, is promising for the rational design of biologically active compounds of nootropic action. Its combination with other heterocyclic fragments, in particular, the 1,2,4-triazole ring, allows for these "hybrid" molecules to expect a permanent change in the magnitude of the pharmacological effects. Creation of a virtual library of compounds, 3D-pharmacophore screening and molecular docking is a promising way to optimize a targeted search for substances with a given pharmacological activity. The aim. To optimize targeted search for new nootropic compounds. Materials and methods. The base generation for the virtual screening was carried out using the Marvin Sketch 20.5 software. For receptor-oriented flexible docking, the Autodock 4.2 software package was used. Results. New derivatives of 1-benzyl-4-pyrrolidin-2-one were selected as the object of the study. Based on the results of the 3D pharmacophore screening and molecular docking to nootropic targets of the virtual base compounds, scoring functions were calculated. A detailed analysis of the geometrical arrangement of "hit compounds" at the active sites of nootropic receptors (PDB ID: 5UOW, 5CXV, 6PV7) made it possible to formulate hypotheses regarding possible ways of interaction of "hybrid" compounds with biotargets. The activity of promising molecules with respect to the studied receptors can be realized by creating complexes between them, the stability of which is ensured mainly due to the energetically favourable geometric arrangement of ligands in the active center of these acceptors, the formation of hydrogen bonds between them, and intermolecular electrostatic and donor-acceptor interactions. Conclusions. Structural modification of the pyrrolidine ring by combining with 1,2,4-triazole scaffold containing substituents of various electronic nature has been proposed. Using 3D-pharmacophore screening, the virtual base of 1-benzyl-4-pyrrolidin-2-one derivatives was analyzed in order to search among them for new molecules of nootropic action. Docking studies have identified a promising group of derivatives of 1-benzyl-4 (4-R-5sulfanylidene-4,5 dihydro-1H-1,2,4-triazol-3-yl) pyrrolidin-2-one, which have affinity for nootropic biotargets and are promising for further synthetic and pharmacological studies
Abstract. The article analyzes the historical process and factors contributing to the formation and development of the substance over form principle in both domestic and global accounting practice, its impact on doing business in specific countries and in international business. The organization and maintenance of accounting is based on a set of accounting principles that should ensure that economic events are properly accounted for and, as a result, converted into financial statements, which serve as a source of information for management decisions by various users of financial and economic information, international entities among them. Among these principles we can name the one of the substance over form. The philosophical basis for defining and applying the substance over form principle has been studied. It is discovered that the definition of the substance over form principle combines dialectically incompatible concepts. Namely, a set of internal, stable and defining links reflecting the main features and development trends of objects and processes (in this case, accounting and financial reporting in business transactions) prevails over the mode of existence and expression of meaning, organization and structure of accounting and financial statements. Such a combination of dialectically incompatible categories may lead to different interpretations of the substance of accounting records and, as a result, of the content of the financial statements. Cases of applying and using the substance over the form principle both in normative documents and in real-life accounting are considered. The main advantages and disadvantages of the application of the substance over form principle in the theory and practice of accounting while performing financial and economic activities and doing international business are analyzed. The research has shown that the application of the substance over form principle increases subjectivity in accounting and is largely determined by the qualifications of the accountant doing professional judgment and their moral and ethical qualities. The main causes of conflict situations while applying the substance over form principle are identified and ways to overcome the existing contradictions arising in the process of reflecting economic events in accounting between their legal (documentary) design and economic content are suggested. Keywords: methodology, principle, substance, content, form, accounting, international business, international relations. JEL Classification B41, M41, F23, F50 Formulas: 0; fig.: 0; tabl.: 1; bibl.: 25.
A series of 3-substituted guinazolinone derivatives have been synthesized in good to excellent yields and high selectivity by one-pot reaction using anthranilic acid, amine and orthoester in ethanol under mild conditions, respectively. The reaction was efficiently promoted by Bi(OTf)3 and the catalyst could be recovered easily after the reactions and reused without evident loss of reactivity. Docking studies have shown that the tested molecules have an affinity for anticancer targets. The data obtained can be used in planning experimental screening for antitumor activity.
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