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

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.