title: Structure guided inhibitor designing of CDK2 and discovery of potential leads against cancer.
abstract: On the basis of stereo specific information obtained from crystal structures of CDK2, indole and chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked with target protein for calculating binding affinities. The binding affinities are represented in glide score. (5E)-5-[(1-methyl-1H-indol-3-yl)methylidene]-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I1), (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were selected for synthesis and biological testing based on vital interactions. (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide(I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were proved to be active against MCF-7 and HeLa cell lines.
authors.affiliation: Department of S & H (Computer Applications), Sathyabama University, Chennai, India. akva1234@gmail.com
authors.forename: Arun V A
authors.initials: AV
authors.lastname: Kumar
authors.forename: Keshav
authors.initials: K
authors.lastname: Mohan
authors.forename: Syed
authors.initials: S
authors.lastname: Riyaz
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D001578:Benzopyrans / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D002625:Chemistry, Organic; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D055808:Drug Discovery; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D007211:Indoles; D047428:Protein Kinase Inhibitors; C030374:indole; D051357:Cyclin-Dependent Kinase 2