Biomaterial Database

QSAR study of PETT derivatives as potent HIV-1 reverse transcriptase inhibitors. 2009

Razieh Sabet, and Afshin Fassihi, and Behzad Moeinifard

Department of Medicinal Chemistry, Faculty of Pharmacy, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran.

A series of phenylethylthiazolylthiourea (PETT) derivatives was subjected to quantitative structure-activity relationship (QSAR) analysis to find the structural requirements for ligand binding. The structural invariants used in this study were those obtained from whole molecular structures: chemical, quantum, topological, geometrical, constitutional and functional groups. Four chemometrics methods including multiple linear regressions (MLRs), factor analysis-MLR (FA-MLR), principal component regression analysis (PCRA) and partial least squares combined with genetic algorithm for variable selection (GA-PLS) were employed to make connections between structural parameters and enzyme inhibition. Using the pool of all types of calculated descriptors a QSAR model was derived for selected calibration set compounds indicating the importance of geometrical and chemical parameters on the Human Immunodeficiency Virus Type-1 (HIV-1) reverse transcriptase inhibitory activity. The results of FA-MLR analysis revealed the effects of geometrical and chemical indices on the inhibitory activity too. GA-PLS analysis showed the constitutional and geometrical indices to be the most significant parameters on inhibitory activity. A comparison between the different statistical methods employed indicated that PCRA represented superior results and it could explain and predict 74% and 79% of variances in the pIC(50) data, respectively.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D013844	Thiazoles	Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms.	Thiazole
D014230	Triazoles	Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.	Triazole
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D054303	HIV Reverse Transcriptase	A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.	Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
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