Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states

Alzate-Morales, JH; Tiznado, W; Santos, JC; Cárdenas C; Contreras R.

Abstract

We report a theoretical study on a series of CDK2 inhibitors using a set of global reactivity indices defined in terms of the density of states. The statistical analysis was performed on the basis of two groups of 11 and 6 compounds, respectively, reported by Hardcastle et al. (J. Med. Chem. 2004, 47, 3710-3722). Both series were classified on the basis of the correlations obtained for the complete set of compounds and the sites targeted within the active site of CDK2. The comparison between the biological activity and the electronic chemical potential approached as the Fermi level yields poor results, thereby suggesting that the interaction between the hinge region (HR) of CDK2 and the ligands may have a marginal contribution from the charge transfer (CT) component. Comparison between the biological activity and global softness shows a better correlation, thereby suggesting that polarization effects outweigh the CT contribution in the HR-ligand interaction. We stress the importance to include in the evaluation of the reactivity indices all of the occupied energy states in order to assess the effects coming from the internal electronic structure involved in the HR-ligand interaction. © 2007 American Chemical Society.

Más información

Título según WOS: Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states
Título según SCOPUS: Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states
Título de la Revista: JOURNAL OF PHYSICAL CHEMISTRY B
Volumen: 111
Número: 12
Editorial: AMER CHEMICAL SOC
Fecha de publicación: 2007
Página de inicio: 3293
Página final: 3297
Idioma: English
URL: http://pubs.acs.org/doi/abs/10.1021/jp064549h
DOI:

10.1021/jp064549h

Notas: ISI, SCOPUS