Multidimensional QSAR Modeling of Amprenavir Derivatives as HIV-Protease Inhibitors

Sonal Dubey, G. Gowtham

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DOI: 10.4236/ojmc.2011.11001                

Abstract

A computational study has been performed on a series of 55 compounds having (S)-N-(3-(N-(cyclopean- tylmethyl)substituted-phenylsulfonamido)-2-hydroxypropyl)acetamide backbone as HIV-1 protease inhibitors. Various combinations of these specific inhibitors fragments were formed by breaking them at central alicyclic single bonds, while retaining the core. Standard Topomer 3D models were automatically constructed for each fragment, and a set of steric and electrostatic fields was generated for each set of topomers. The models generated showed r² of 0.811 and crossvalidated r² (q²) of 0.608. The other method used were Quasar and Raptor based on receptor-modelling concept (6D-QSAR) and this explicitly allows for the simulation of the induced fit, that yielded r² of 0.574, cross-validated r² (q²) of 0.504 and predictive r² (q²) of 0.895 averaged over 200 models. This study has suggested the various type of substituent that can be attached to the core. The information obtained from these 3-D contour maps can be used for the design of amprenavir analogs possessing better protease inhibitory activity.

Keywords

3D-QSAR, 5D-QSAR, 6D-QSAR, Topmer CoMFA, Quasar, Raptor

Conflicts of Interest

The authors declare no conflicts of interest.

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