title: 3D-QSAR CoMFA study on oxindole derivatives as cyclin dependent kinase 1 (CDK1) and cyclin dependent kinase 2 (CDK2) inhibitors.
abstract: Cyclin dependent kinases have emerged as important drug targets with a multitude of therapeutic potentials for their inhibitors. With the purpose of designing new chemical entities with enhanced inhibitory potencies against cyclin dependent kinase 2 (CDK2) and cyclin dependent kinase 1 (CDK1), the 3D-QSAR CoMFA study carried out on oxindole derivatives as inhibitors of these kinases is presented here. The developed model showed a good correlative and predictive ability having a cross validated correlation co-efficient of 0.518 for CDK1 and 0.613 for CDK2. The conventional and predictive correlation coefficients were found to be respectively 0.943 and 0.508 for CDK1 and 0.957 and 0.585 for CDK2. The models could be usefully employed to design dual CDK1 and CDK2 inhibitors and/or to find novel scaffolds through screening of chemical databases.
authors.affiliation: Centre of Excellence in Bioinformatics, School of Biotechnology, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India. sanjeevsky@rediffmail.com
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Nigus
authors.initials: N
authors.lastname: Dessalew
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D016018:Least-Squares Analysis; D008024:Ligands; D008958:Models, Molecular; D000078183:Oxindoles; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008024:Ligands; D000078183:Oxindoles; C022960:2-oxindole; D000255:Adenosine Triphosphate; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2