3-D QSAR studies on histone deacetylase inhibitors. A GOLPE/GRID approach on different series of compounds

Rino Ragno; Silvia Simeoni; Sergio Valente; Silvio Massa; Antonello Mai

doi:10.1021/ci050556b

3-D QSAR studies on histone deacetylase inhibitors. A GOLPE/GRID approach on different series of compounds

J Chem Inf Model. 2006 May-Jun;46(3):1420-30. doi: 10.1021/ci050556b.

Authors

Rino Ragno¹, Silvia Simeoni, Sergio Valente, Silvio Massa, Antonello Mai

Affiliation

¹ Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy. [email protected]

PMID: 16711762
DOI: 10.1021/ci050556b

Abstract

Docking simulation and three-dimensional quantitative structure-activity relationships (3D-QSARs) analyses were conducted on four series of HDAC inhibitors. The studies were performed using the GRID/GOLPE combination using structure-based alignment. Twelve 3-D QSAR models were derived and discussed. Compared to previous studies on similar inhibitors, the present 3-D QSAR investigation proved to be of higher statistical value, displaying for the best global model r2, q2, and cross-validated SDEP values of 0.94, 0.83, and 0.41, respectively. A comparison of the 3-D QSAR maps with the structural features of the binding site showed good correlation. The results of 3D-QSAR and docking studies validated each other and provided insight into the structural requirements for anti-HDAC activity. To our knowledge this is the first 3-D QSAR application on a broad molecular diversity training set of HDACIs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Histone Deacetylase Inhibitors*
Models, Molecular
Quantitative Structure-Activity Relationship

Substances

Enzyme Inhibitors
Histone Deacetylase Inhibitors