A quantitative structure-activity relationships study for the anti-HIV-1 activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives using the multiple linear regression and partial least squares methodologies

A quantitative structure-activity relationships (QSAR) study using Multiple Linear Regression (MLR) and Partial Least Squares (PLS) methodologies was performed for a series of 127 derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), a potent inhibitor of the of the human immunodeficiency virus type 1, HIV-1 reverse transcriptase (RT). The MLR and PLS methods were employed to explore the relationship between the descriptors (as independent variables) of a pool of HEPT derivative and anti-HIV-1 activity, expressed as log (1/EC50) (as dependent variables). Using Dragon descriptors, the present study was aimed at developing a predictive and robust QSAR model for predicting anti-HIV activity of HEPT derivatives for a better understanding of the molecular features of these compounds important for their biological activity. According to the squared correlation coefficients, which had values between 0.826 and 0.809 for the MLR and PLS methods, the results demonstrated almost identical qualities and good predictive ability for both the MLR and PLS models. After dividing the dataset into training and test sets, the model predictability was tested by several parameters, including the Golbraikh-Tropsha external criteria and the goodness of fit, tested using the Y-randomization test.