Docking and three-dimensional quantitative structure–activity relationship analyses of imidazole and thiazolidine derivatives as Aurora A kinase inhibitors
Autor: | Chaeuk Im |
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Rok vydání: | 2016 |
Předmět: |
Models
Molecular 0301 basic medicine Quantitative structure–activity relationship Stereochemistry Thiazolidine Aurora A kinase Quantitative Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Imaging Three-Dimensional 0302 clinical medicine Drug Discovery Imidazole Protein Kinase Inhibitors Mitotic catastrophe Aurora Kinase A Binding Sites Organic Chemistry Imidazoles Biological activity Molecular Docking Simulation 030104 developmental biology chemistry Biochemistry Docking (molecular) 030220 oncology & carcinogenesis Thiazolidines Molecular Medicine |
Zdroj: | Archives of Pharmacal Research. 39:1635-1643 |
ISSN: | 1976-3786 0253-6269 |
Popis: | Aurora A kinase is involved in the inactivation of apoptosis leading to ovarian, breast, colon, and pancreatic cancers. Inhibitors of Aurora A kinase promote aberrant mitosis resulting in arrest at a pseudo G1 state to induce mitotic catastrophe, ultimately leading to apoptosis. In this study, ligand-based and docking-based three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses of imidazole and thiazolidine derivatives as potential Aurora A kinase inhibitors were performed. The results provided highly reliable and predictive 3D-QSAR comparative molecular similarity index analysis (CoMSIA) models with a cross-validated q2 value of 0.768, non-cross-validated r2 value of 0.983, and predictive coefficient [Formula: see text] value of 0.978. CoMSIA contour maps suggested that the NH and benzyl hydroxy groups in R9, and the CO group in the thiazolidine ring and pyridine ring were important components for biological activity. The maps also suggest that the introduction of hydroxy groups at C2 of the imino-phenyl ring, C5 in the pyridine ring, or the substitution of the imino-phenyl ring for the imino-2-pyridine ring could be applied to enhance biological activity. |
Databáze: | OpenAIRE |
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