Therortical Studies and Investagting of Selected Potnet CDK2 Inhibitors as Anticancer Agents

Abstract

In this study eight selected of the most potent cyclin dependent kinase 2 inhibitors in which targeting adenosine triphosphate -pocket site theoretically investigated to support literature information of frontier molecular orbitals, molecular electrostatic maps, and global chemical reactivity descriptors such as chemical hardness, chemical softness, chemical potential, electronegativity and electrophilicity of cyclin dependent kinase 2 inhibitors. Calculation and three-dimensional plotting were achieved through Gaussian 09W and Gausview 6 software’s utilizing density functional theory quantum modeling applying both hybrids extended and not extended basis set. Crystal structure of CDK2 with inhibitors was obtained from protein data bank and visualized through PyMol Schrödinger software to assign polar and non-polar interactions of inhibitors with enzyme. A promising conclusion trend obtained in this research regarding to molecules that could have an inhibition activity toward the cyclin dependent kinase 2 enzymes. Our theoretical investigation emphasizes that, the anti-cancer activity has directly relationship with value of chemical hardness and chemical softness, where the most potent compounds was the pyrazolopyrimidine and imidazole pyrimidine and they have higher chemical hardness value and at the same time lower value of chemical softness compared with the rest of compounds.