Comparison Between 2D and 3D-QSAR Approaches to Correlate Inhibitor Activity for a Series of Indole Amide Hydroxamic Acids

摘要

The well-expressed inhibitor activity of 36 indole amide hydroxamic acids to Histone Deacetylases (HDACs) was analyzed by CODESSA PRO software and the Best Multiple Linear Regression (BLMR) algorithm, to provide a reliable 2D-QSAR model from a set of more than 800 descriptors. Concurrently, Chem-X (version 1994) software was used to develop a corresponding 3D-QSAR model; the steric and electrostatic interactions between a fictitious probe atom "H+" and a set of aligned molecules were evaluated using the CoMFA approach as implemented in Chem-X. A Partial Least Squares (PLS) procedure generated the principal components needed to build a 3D-QSAR model. The Weighted Least Squares (WLS) method generated an R2 map of the regions around the molecules important for steric and electrostatic interactions. Enzyme - inhibitor docking calculations were carried out to combine and compare with the results obtained by CoMFA. New potentially active structures were proposed.