QSAR and docking studies on the pyrimidine derivatives analogs with antileishmanial activity

Abstract

Leishmaniasis is a disease caused by a number of species of protozoan parasites belonging to the genus Leishmania, is recognized as an important public health problem throughout the world. In a search of newer and potent antileishmanial drug, a series of 30 pyrimidine derivatives analogs were subjected to a quantitative structure activity relationship (QSAR) analysis, for studying, interpreting, and predicting activities and designing new compounds by using several statistical tools, such as principal components analysis (PCA), multiple linear regression (MLR) and non-linear regression (RNLM). The statistical results of the MLR and MNLR indicate that the determination coefficients R 2 were 0.824 and 0.870, respectively. Internal and external validations were used to determine the statistical quality and predictive power of QSAR of the two MLR and MNLR models. The applicability domains of MLR and MNLR models were investigated using William’s plot to detect outliers and outsides compounds. Also the most active compounds were docked into the active site of the protein (PDB entry code: 2JK6) to confrm those obtained results from QSAR models and identify the binding interactions responsible for antileishmanial activity of those analogs.