Docking-based 3D-QSAR study of HIV-1 integrase inhibitors.
In this study, 3-aroyl-1,1-dioxo-1,4,2-benzodithiazine and 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives (HIV-1 integrase inhibitors) were used for CoMFA and CoMSIA to determine the substructures required for the activity of these molecules. To explore the binding mode of inhibitors, docking studies were done and docked conformation of highly active molecule was used as template for alignment. The best CoMFA model yielded the cross validation r(2)(cv)=0.728, non-cross validation r(2)(ncv)=0.934 and predictive r(2)(pred)=0.708. The best CoMSIA model yielded a cross validation r(2)(cv)=0.794, non-cross validation r(2)(ncv)=0.928 and predictive r(2)(pred)=0.59. It was found that steric (CoMFA) and hydrophobic fields (CoMSIA) have large contribution towards the inhibitory activity than the other fields. Docking and 3D-QSAR studies have provided clues to a better understanding of interaction between the inhibitors and HIV-1 integrase.
Gupta
Pawan
P
Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, SAS Nagar, 160062 Punjab, India.
Roy
Nilanjan
N
Garg
Prabha
P
D020134:Catalytic Domain; D003198:Computer Simulation; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
D019428:HIV Integrase Inhibitors; D013449:Sulfonamides; D019427:HIV Integrase; D008274:Magnesium; C514801:p31 integrase protein, Human immunodeficiency virus 1