Özet:

The aim of the work. To fulfill QSAR analysis of antioxidant activity for the series of N3 substituted 3H-thiazolo[4,5-b]pyridine-2-one derivatives in order to reveal the objective characteristics of "structure - antioxidant activity" correlation and the theoretical backgrounds development for the directed synthesis of potential "drug-like" molecules among the derivatives of the above-mentioned class of compounds. To estimate the statistical quality and predictive ability of the obtained models. Materials and Methods: molecular descriptors calculation, systematic search algorithm for an optimal set of descriptors, multiple linear regression, QSAR analysis. Results and Discussion. QSAR analysis for the antioxidant activity of 29 novel 3H-thiazolo[4,5-b]pyridine-2-one derivatives was performed. According to the QSAR analysis results, it was determined that antioxidant activity of the compounds under study depends mainly on descriptors that determine two-dimensional (2D) and spatial (3D) structure of their molecules. A series of two- and three-variables QSAR models were obtained. The interpretation of these models shows that the free radical scavenging activity of compounds increases with the presence of certain functional groups and structural fragments in their molecules, in particular, the presence of structural fragments with the sum of topological distances equal to 2, in the molecules of substances, whose terminal atoms have high electronegativity values, is undesirable. The higher value of antioxidant activity corresponds to the minimum redistribution of charges between each pair of atoms in the molecule located at the topological distance of 6. The activity of the compounds also increases when the heavy atoms are in the molecular space closer to the center of the molecule, with the preference given to the pairs of heavy atoms, the topological distance between which is equal to 6. The activity of substances enhancing occurs if the scattering of the electrons beam by a group of atoms will occur mainly due to atoms with high electronegativity. The linear relationship between the activity of compounds and the 3D molecular distribution of atomic masses, electronegativity and the ability for polarization in spherical volumes with the radii of 7.0-7.5 Å and 14.0-15.0 Å. was also proved. Conclusions. The high statistical quality and predictive ability of the two- and three-parameter QSAR models obtained certify the possibility of their further application for the virtual screening of compounds libraries for identifying novel antioxidant agents based on the same congeneric series.     «Publications are based on the research provided by the grant support of the State Fund For Fundamental Research (project N 31411)»

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