Molecular modeling studies of N-substituted pyrrole derivatives--potential HIV-1 gp41 inhibitors.

2D-, 3D-QSAR and docking studies were carried out on 23 pyrrole derivatives, to model their HIV-1 gp41 inhibitory activities. The 2D, 3D-QSAR studies were performed using CODESSA software package and comparative molecular field analysis (CoMFA) technique, respectively. The CODESSA five-descriptor model has a correlation coefficient R(2)=0.825 and a standard deviation s(2)=0.132. The 3D-QSAR CoMFA study allowed to obtain a model showing a good correlative and predictive capability which statistical results, provided by a eight-component regression equation, are: R(2)=0.984, q(2)=0.463, s=0.119. Docking studies were employed to determine probable binding conformation of these analogues into the gp41 active site using the AutoDock program whose results were found complementary with thus of 2D- and 3D-QSAR analysis. These findings provide guidance for the design and structural modifications of these derivatives for better anti-HIV-1 activity which is important for the development of a new class of entry inhibitors.