Biomaterial Database

Docking-based CoMFA and CoMSIA study of azaindole carboxylic acid derivatives as promising HIV-1 integrase inhibitors. 2013

S Yu, and P Wang, and Y Li, and Y Liu, and G Zhao

a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Shandong , China.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed based on a series of azaindole carboxylic acid derivatives that had previously been reported as promising HIV-1 integrase inhibitors. Docking studies to explore the binding mode were performed based on the highly active molecule 36. The best docked conformation of molecule 36 was used as template for alignment. The comparative molecular field analysis (CoMFA) model (including steric and electrostatic fields) yielded the cross validation q (2) = 0.655, non-cross validation r (2) = 0.989 and predictive r (2) pred = 0.979. The best comparative molecular similarity indices analysis (CoMSIA) model (including steric, electrostatic, hydrophobic and hydrogen-bond acceptor fields) yielded the cross validation q (2) = 0.719, non-cross validation r (2) = 0.992 and predictive r (2) pred = 0.953. A series of new azaindole carboxylic acid derivatives were designed and the HIV-1 integrase inhibitory activities of these designed compounds were predicted based on the CoMFA and CoMSIA models.

UI	MeSH Term	Description	Entries
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D002264	Carboxylic Acids	Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic.	Carboxylic Acid,Acid, Carboxylic,Acids, Carboxylic
D015497	HIV-1	The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.	Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D062105	Molecular Docking Simulation	A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.	Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking
D019427	HIV Integrase	Enzyme of the HUMAN IMMUNODEFICIENCY VIRUS that is required to integrate viral DNA into cellular DNA in the nucleus of a host cell. HIV integrase is a DNA nucleotidyltransferase encoded by the pol gene.	HIV Integration Protein,p31 Integrase Protein, HIV,p31 Integrase Protein, Human Immunodeficiency Virus,p31 pol Gene Product, HIV,p31 pol Gene Product, Human Immunodeficiency Virus,Integrase, HIV,Integration Protein, HIV
D019428	HIV Integrase Inhibitors	Inhibitors of HIV INTEGRASE, an enzyme required for integration of viral DNA into cellular DNA.	Integrase Inhibitors, HIV,Inhibitors, HIV Integrase
D021281	Quantitative Structure-Activity Relationship	A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.	Structure Activity Relationship, Quantitative,3D-QSAR,QSAR,QSPR Modeling,Quantitative Structure Property Relationship,3D QSAR,3D-QSARs,Modeling, QSPR,Quantitative Structure Activity Relationship,Quantitative Structure-Activity Relationships,Relationship, Quantitative Structure-Activity,Relationships, Quantitative Structure-Activity,Structure-Activity Relationship, Quantitative,Structure-Activity Relationships, Quantitative