title: Molecular modeling studies of 4,5-dihydro-1H-pyrazolo[4,3-h] quinazoline derivatives as potent CDK2/Cyclin a inhibitors using 3D-QSAR and docking.
abstract: CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r(2) (cv) values of 0.747 and 0.518 and r(2) values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.
authors.affiliation: Laboratory for Natural Product Chemistry, College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China; E-Mails: aiyong0508@126.com (Y.A.); wst418638862@sohu.com (S.-T.W.).
authors.forename: Yong
authors.initials: Y
authors.lastname: Ai
authors.forename: Shao-Teng
authors.initials: ST
authors.lastname: Wang
authors.forename: Ping-Hua
authors.initials: PH
authors.lastname: Sun
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Song
mesh_terms: D000595:Amino Acid Sequence; D019925:Cyclin A / Q000737:chemistry* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D019925:Cyclin A; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D051357:Cyclin-Dependent Kinase 2