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

Jans H. Alzate-Morales, William Tiznado, Juan C. Santos, Carlos Cárdenas, Renato Contreras

Resultado de la investigación: Article

8 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)3293-3297
Número de páginas5
PublicaciónJournal of Physical Chemistry B
Volumen111
N.º12
DOI
EstadoPublished - 29 mar 2007

Huella dactilar

softness
hinges
Hinges
inhibitors
Ligands
activity (biology)
Bioactivity
ligands
Charge transfer
reactivity
charge transfer
Chemical potential
interactions
Fermi level
statistical analysis
Electron energy levels
Electronic structure
Statistical methods
Polarization
electronic structure

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Citar esto

Alzate-Morales, Jans H. ; Tiznado, William ; Santos, Juan C. ; Cárdenas, Carlos ; Contreras, Renato. / Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states. En: Journal of Physical Chemistry B. 2007 ; Vol. 111, N.º 12. pp. 3293-3297.
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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.",
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Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states. / Alzate-Morales, Jans H.; Tiznado, William; Santos, Juan C.; Cárdenas, Carlos; Contreras, Renato.

En: Journal of Physical Chemistry B, Vol. 111, N.º 12, 29.03.2007, p. 3293-3297.

Resultado de la investigación: Article

TY - JOUR

T1 - Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states

AU - Alzate-Morales, Jans H.

AU - Tiznado, William

AU - Santos, Juan C.

AU - Cárdenas, Carlos

AU - Contreras, Renato

PY - 2007/3/29

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N2 - 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.

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