title: 3D-QSAR and molecular docking studies of azaindole derivatives as Aurora B kinase inhibitors.
abstract: The Aurora kinases have been regarded as attractive targets for the development of new anticancer agents. Recently a series of azaindole derivatives with Aurora B inhibitory activities were reported. To explore the relationship between the structures of substituted azaindole derivatives and their inhibition of Aurora B, 3D-QSAR and molecular docking studies were performed on a dataset of 41 compounds. 3D-QSAR, including CoMFA and CoMSIA, were applied to identify the key structures impacting their inhibitory potencies. The CoMSIA model showed better results than CoMFA, with r(2)(cv) value of 0.575 and r(2) value of 0.987. 3D contour maps generated from CoMFA and CoMSIA along with the docking binding structures provided enough information about the structural requirements for better activity. Based on the structure-activity relationship revealed by the present study, we have designed a set of novel Aurora B inhibitors that showed excellent potencies in the developed models. Thus, our results allowed us to design new derivatives with desired activities.
authors.affiliation: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lan
authors.forename: Wan-Na
authors.initials: WN
authors.lastname: Chen
authors.forename: Ping-Hua
authors.initials: PH
authors.lastname: Sun
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D001372:Aza Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D001372:Aza Compounds; D007211:Indoles; D047428:Protein Kinase Inhibitors; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases