Collect. Czech. Chem. Commun. 2011, 76, 1447-1469
Published online 2011-12-04 18:33:05

Docking alignment-3D-QSAR of a new class of potent and non-chiral indole-3-carboxamide-based renin inhibitors

Jahan B. Ghasemi* and Somayeh Pirhadi

Chemistry Department, Faculty of Sciences, K. N. Toosi University of Technology, Tehran, Iran


Using generated conformations from docking analysis by CDOCKER algorithm, some 3D-QSAR models; CoMFA region focusing (CoMFA-RF) and CoMSIA have been created on a series of a new class of potent and non-chiral renin inhibitors. The satisfactory predictions were obtained by CoMFA-RF and CoMSIA based on docking alignment in comparison to CoMFA. Robustness and predictability of the models were further verified by using the test set, cross validation (leave one out and leave ten out), bootstrapping, and progressive scrambling. All-orientation search (AOS) strategy was used to acquire the best orientation and minimize the effect of the initial orientation of aligned compounds. The results of 3D-QSAR models are in agreement with docking results. Moreover, the resulting 3D CoMFA-RF/ CoMSIA contour maps and corresponding models were applied to design new and more active inhibitors.

Keywords: Enzymes; Drug design; Drug discovery; CoMFA; CoMSIA; CDOCKER; Realignment; Renin inhibitors.

References: 39 live references.