QSAR studies of histone deacetylase (HDAC) inhibitors by CoMFA, CoMSIA, and molecular docking

In order to develop highly potent antitumor agents, three-dimensional quantitative structure-activity relationship (3-D QSAR) studies were conducted using a series of thienyl-based hydroxamic acids. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were applied to provide the structural information for further chemical modification and optimization. ClogP was applied as an additional descriptor in the CoMFA analysis to study the effects of lipophilic parameters on the activity of these compounds, and it did improve the statistical significance of the model. Two molecules were designed based on the 3-D QSAR analysis, their activity values were predicted by the generated model, and their binding mode was elucidated by a docking approach compared to molecules in the dataset.