QSAR ANALYSIS OF ANTIOXIDANT ACTIVITY FOR NOVEL CONDENSED 4-AZOLIDONE BASED DERIVATIVES
DOI:
https://doi.org/10.11603/2312-0967.2018.3.9376Keywords:
thiazolo[4, 5-b]pyridine-2-ones, QSAR analysis, biological acivity evaluation, molecular descriptors.Abstract
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)»
References
Chaban TI, Ogurtsov VV, Chaban IG, Klenina OV, Komarytsia JD. Synthesis and antioxidant activity evaluation of novel 5,7-dimethyl-3H-thiazolo[4,5-b]pyridines. Phosphorus, Sulfur Silicon Relat. Elem. 2013;188:1611-20.
Klenina O, Drapak I, Chaban T, Ogurtsov V, Chaban I, Golos I. QSAR studies of some thiazolo[4,5-b]pyridines as novel antioxidant agents: enhancement of activity by some molecular structure parameters. Сhem. & Chem. Techn. 2013;7:397-404.
Klenina O, Chaban T, Zimenkovsky B, Harkov S, Ogurtsov V, Chaban I [et al.]. QSAR modeling for antioxidant activity of novel N3 substituted 5,7-dimethyl-3Н-thiazolo[4,5-b]pyridin-2-ones. Pharmacia. 2017;64(4):49-71.
Chaban T, Klenina O, Harkov S, Ogurtsov V, Chaban I, Nektegaev I. Synthesis of some new N3 substituted 6-phenylazo-3Н-thiazolo[4,5-b]pyridin-2-ones as possible anti-inflammatory agents. Pharmacia. 2017;64(4):16-30.
Ogurtsov V, Chaban T, Klenina O., Chaban I, Komarytsia J. In silico approaches towards rational design of anti-inflammatory agents through thiazolopyridine derivatives. Farmacevt chasop. 2013;1:11-22. Ukrainian.
Klenina OV, Chaban TI, Ogurtsov VV, Chaban IG, Golos IYa. 3D Pharmacophore modeling in the milecules of 5,7-dimethyl-6-phenylazo-3Н-thiazolo[4,5-b]pyridine-2-one derivatives. Journal of organic and pharmaceutical chemistry. 2014;1:60-8. Ukrainian.
Chaban TI, Klenina OV, Zimenkovsky BS, Chaban IG, Ogurtsov VV, Shelepeten LS. Synthesis of novel thiazolo[4,5-b]pyridines as potential biologically active substances. Der Pharma Chemica. 2016;8(19):534-42.
Chaban TI, Ogurtsov VV, Chaban IG, Lebyak MM, Nektegaev IO. Synthesis and anti-exudative activity evaluation 6-amino-5,7-dimethyl-3Н-thiazolo[4,5-b]pyridine-2-one and its 6 arylidene amino derivatives. Farmacevt chasop. 2011; 2: 10-14. Ukrainian.
Chaban T, Klenina O, Drapak I, Ogurtsov V, Chaban I, Novikov V. Synthesis of some novel thiazolo[4,5-b]pyridines and their tuberculostatic activity evaluation.Сhem. & Chem. Techn. 2014;89:287-92.
Chaban TI, Ogurtsov VV, Chaban IG, Konarytsia JD. Synthesis and anti-microbial activity evaluation of some thiazolo[4,5-b]pyridines. Journal of organic and pharmaceutical chemistry. 2012;2:70-6. Ukrainian.
Chaban TI, Panchuk RR, Klenina OV, Skorokhyd NR, Ogurtsov VV, Chaban IG. Synthesis and evaluation of antitumor activity of some thiazolo[4,5-b] pyridines. Biopolymers and Cell. 2012;28:389-96.
Gu L, Jin C. Synthesis and antitumor activity of α-minophosphonates containing thiazole[5,4-b]pyridine moiety. Org. Biomol. Chem. 2012;10:7098-7102.
Kulkarni SS, Newman AH. Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists. Bioorg. Med. Chem. Lett. 2007;17:2987-91.
Lin R, Johnson SG, Connolly PJ, Wetter SK, Binnun E, Hughes TV [et al.] Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d] pyrimidine analogues as anti-tumor epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett. 2009;19:2333-7.
Komoriya S, Kobayashi S, Osanai K, Yoshino T, Nagata T, Haginoya N [et al.] Design, synthesis, and biological activity of novel factor Xa inhibitors: improving metabolic stability by S1 and S4 ligand modification. Bioorg. Med. Chem. 2006;14:1309-30.
Singh B, Bacon ER, Lesher ER, Robinson S, Pennock PO, Bode DC [et al.]. Novel and potent adenosine 3',5'-cyclic phosphate phosphodiesterase III inhibitors: Thiazolo[4,5-b][1,6]naphthyridin-2-ones. J. Med. Chem. 1995;38:2546-50.
HuperCube, Inc.: http://www.hyper.com HyperChem software. HuperCube, Inc. 1115 NW 4th Street, Gainesville, Fl 32601 USA http://www.hyper.com.
Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, et al. Virtual computational chemistry laboratory - design and description. J. Comput. Aid. Mol. Des. 2005;19:453-63.
VCCLAB, Virtual computational chemistry laboratory, http://www.vcclab.org, 2005.
de Oliviera DB, Gaudio AC. BuiltQSAR: A new computer program for QSAR analysis . Quantitative Structure – Activity Relationships. 2000; 19 ( 6): 599-601.
Suleiman MM, Isaev SG, Klenina OV, Ogurtsov VV. Synthesis, biological activity evaluation and QSAR studies of novel 3-(aminooxalyl-amino)- and 3-(carbamoyl-propionylamino)-2-phenylamino-benzoic acid derivatives. J.Chem.Pharm.Res. 2014;6(5):1219-35.
Helguera AM, Combes RD, Gonzalez MP, Cordeiro MN. Application of 2D Descriptors in Drug Design: A DRAGON Tale. Curr. Top. Med. Chem. 2008;8(18):1628-55.
Todeschini R, Consonni V. Molecular descriptors for chemoinformatics. Weinheim (Germany): WILEY-VCH; 2009. 1257 p.
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