title: Multicomplex-based pharmacophore-guided 3D-QSAR studies of N-substituted 2'-(aminoaryl)benzothiazoles as Aurora-A inhibitors.
abstract: Aurora-A has been known as one of the most important targets for cancer therapy, and some Aurora-A inhibitors have entered clinical trails. In this study, combination of the ligand-based and structure-based methods is used to clarify the essential quantitative structure-activity relationship of known Aurora-A inhibitors, and multicomplex-based pharmacophore-guided method has been suggested to generate a comprehensive pharmacophore of Aurora-A kinase based on a collection of crystal structures of Aurora-A-inhibitor complex. This model has been successfully used to identify the bioactive conformation and align 37 structurally diverse N-substituted 2'-(aminoaryl)benzothiazoles derivatives. The quantitative structure-activity relationship analyses have been performed on these Aurora-A inhibitors based on multicomplex-based pharmacophore-guided alignment. These results may provide important information for further design and virtual screening of novel Aurora-A inhibitors.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No.1 Keyuan Road 4, Gaopeng Street, Chengdu, 610041, China. hegu@scu.edu.cn
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.forename: Minghua
authors.initials: M
authors.lastname: Qiu
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Ouyang
authors.forename: Fengbo
authors.initials: F
authors.lastname: Wu
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.forename: Luoting
authors.initials: L
authors.lastname: Yu
mesh_terms: D064127:Aurora Kinases; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship
chemical_list: D052160:Benzothiazoles; D047428:Protein Kinase Inhibitors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases