title: Identification of new novel scaffold for Aurora A inhibition by pharmacophore modeling and virtual screening.
abstract: Aurora kinases belong to family of highly conserved serine/threonine protein kinases that are involved in diverse cell cycle events and play a major role in regulation of cell division. Abnormal expression of Aurora kinases may lead to cancer; hence, these are considered as a potential target in cancer treatment. In this research article, we identified three novel Aurora A inhibitors using modern computational tools. A four-point common 3D pharmacophore hypothesis of Aurora A (AurA) inhibitors was developed using a diverse set of 55 thienopyrimidine derivatives. A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out using atom-based alignment of diverse set of 55 molecules to evaluate the structure- activity relationships. Docking and 3D-QSAR studies were performed with the 3D structure of AurA to evaluate the generated pharmacophore. The pharmacophore model and 3D-QSAR results complemented the results of our docking study. The pharmacophore hypothesis, which yields the best results, was used to screen the Zinc 'clean drug-like' database. Various database filters such as 3D-arrangement of pharmacophoric features, predicted activity and binding interaction score were used to retrieve hits having potential AurA inhibition activity.
authors.affiliation: CSIR Unit for Research and Development of Information Products, "Jopasana", 85/1, Paud Road, Kothrud, Pune, 411038, India, sayalee@urdip.res.in.
authors.forename: Sayalee R
authors.initials: SR
authors.lastname: Chavan
authors.forename: Radha Charan
authors.initials: RC
authors.lastname: Dash
authors.forename: M Sarwar
authors.initials: MS
authors.lastname: Alam
authors.forename: Raj R
authors.initials: RR
authors.lastname: Hirwani
mesh_terms: D064096:Aurora Kinase A / Q000037:antagonists & inhibitors*; D066264:Datasets as Topic; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D064096:Aurora Kinase A
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