Computational Modeling of Substitution Effect on HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Kier- Hall Electrotopological State (E-state) Indices
BioChem Press, Nitin S. Sapre, Nilanjana Pancholi, Swagata Gupta · 2008
Motivation The application of Kier–Hall electrotopological state (E–state) indices has helped in deriving mathematical models, where the electronic attributes of an atom in a chemical graph could be encoded as an index. By changing a substituent in a molecule, a corresponding change in its E–state value as well as physicochemical/biological properties is observed. With the help of Kier–Hall electrotopological indices, the effect of substituent could be analyzed and subsequently used in modeling the inhibitory activity of HIV–1 non– nucleoside reverse transcriptase inhibitors (NNRTIs). The applicability of Kier–Hall E–state indices can provide a new insight to the quantitative structure–activity relationship studies of potential drug compounds. Method. The multiple linear regression (MLR) method is used to generate a predictive model for the training set consisting of a series of 55 derivatives of 2–amino–6–arylsulfonylbenzonitrile (AASBN). The result is cross– validated with the help of a test set. Results. A QSAR model for a series of 55 AASBN derivatives is generated to understand the effect of substitution on their inhibitory activity (n = 55, R = 0.843, R