3D QSAR and docking studies of a series of histone deacetylase inhibitors

Abstract

In recent years, a class of intracellular metalloproteases known as histone deacetylases (HDACs) has become popular targets for cancer therapy. HDACs play an important role in the modification of chromatin structure and regulation of gene expression. In this study, structure-based and ligand-based methods are used to provide a theoretical basis for finding highly potent antitumor drugs. 61 small molecules were studied by three-dimensional quantitative structure–activity relationship (3D QSAR) method. Comparative molecular field analysis and comparative molecular similarity indices analysis methods were employed to build the 3D QSAR model of HDAC inhibitors containing hydroxamic acid group. As the 3D-structure of target HDACs has been investigated by the X-ray crystallographic studies, the binding mode between compounds and HDACs can be explored by docking approach.