QSAR for Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptas

P. R. DUCHOWICZ; M. F. LLAMOSA; J. CABALLERO; E. A. CASTRO; F. M. FERNÁNDEZ

BIOORGANIC & MEDICINAL CHEMISTRY.

Año: 2006 vol. 14 p. 5876 - 5889

0968-0896

By means of QSAR algorithms we model the potency pIC90 [mM] of 154 non-nucleoside reverse transcriptase inhibitors (NNRTI) of the wild-type HIV-1 virus, considered as the second generation analogues of Efavirenz. In addition, 56 inhibitors of the K-103N viral mutant form are also investigated. A pool of 1494 theoretical molecular descriptors provided mainly by the Dragon 5 software is explored by several methods of variable selection: forward stepwise regression, the replacement method, and the geneticalgorithm approach. The optimal models found include up to seven parameters: R=0.7991, Rl-20%-o=0.7233 for the case of wild-type, and R=0.9261, Rl-5%-o=0.8802 for the K-103N mutation