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.
Teixeira
Cátia
C
ITODYS, University Paris 7-CNRS UMR 7086, 1 rue Guy de la Brosse, 75005 Paris, France.
Barbault
Florent
F
Rebehmed
Joseph
J
Liu
Kun
K
Xie
Lan
L
Lu
Hong
H
Jiang
Shibo
S
Fan
BoTao
B
Maurel
François
F
D019380:Anti-HIV Agents / Q000737:chemistry*; D001665:Binding Sites; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D011758:Pyrroles