Abstract
Cyclin-dependent kinase 6 (CDK6) is an important member of protein kinases, involving in many cellular pathways especialy cell cycle progression. Thus, CDK6 is a promising target in cancer therapy. This report aims to predict inhibiton of CDK6 by some complex compounds by using molecular docking and pharmacological properties analysis. Those compounds are isatinyl-2-aminobenzoylhydrazone (ISABH) and cobalt (II), nickel (II), copper (II), and zinc (II) transition metal complexes. The molecular docking against CDK6 (PDB code: 3NUP) revealed that ISABH/ISABH-transition metal complexes established ligand-protein interaction as expressed by negative binding affinity values. Drug-likeness by SwissADME indicated that ISABH and Ni-ISABH met the Lipinski’s rule of five. Both compounds also showed reasonable pharmacological criteria by admetSAR.
Highlights
Kinases are proteins that involved in the cellular pathways such as signal transduction and cell cycle progression mainly through phosphorylation [1]
The present study reports on an attempt to develop Cyclin-dependent kinase 6 (CDK6) inhibitors based on the chemistry of isatin-hydrazone
The cross-docking of ISABH and its complexes with metal ions of cobalt (II), nickel (II), copper (II), and zinc (II) on CDK6 protein (PDB ID: 3NUP) produced binding affinity of -9.4; -8.5; -6.6; -6.5; -5.4 kcal/mol for Ni-ISABH, ISABH, Co-ISABH, Cu-ISABH, and ZnISABH, respectively
Summary
Kinases are proteins that involved in the cellular pathways such as signal transduction and cell cycle progression mainly through phosphorylation [1]. CDK6 gene is located on chromosome 7 in humans extends 231,706 base pairs and involves in cell cycle progression by encoding a 326 amino acids protein [5]. The activity of this kinase is controlled by the D-type cyclins regulatory subunits and CDK inhibitors i.e INK4 family. The pathway of cyclin D-CDK4/6-INK4RB has been observed in several cancer types due to uncontrolled cell cycle/growth [7]. These kinases are being used as a potential target of cancer therapeutic research and development. Palbociclib, a nitrogen-containing heterocyclic compound of CDK4/ CDK6 targeted therapy, is approved for the treatment of breast cancer [8]
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