The influence of electronic and steric effects in the structure–activity relationship (SAR) study of quinone compounds with biological activity against Trypanosoma cruzi

A set of 14 quinone compounds with anti-trypanocidal activity was studied by using the AM1 semi-empirical method in order to calculate atomic and molecular properties (variables or descriptors) to be correlated to the biological activity. Principal component analysis (PCA), hierarchical cluster analysis (HCA), stepwise discriminant analysis (SDA) and the K th nearest neighbor (KNN) method were employed to obtain possible relationships between the calculated descriptors and the biological activity studied and to predict the anti-trypanocidal activity of new quinone compounds from a prediction set. The atomic and molecular descriptors responsible for the separation between the active and inactive compounds were: total energy ( E T ), polarizability ( α ) and the charge on the R 1 atom ( Q 4 ). These descriptors give information on the kind of interaction that can occur between the compounds and the biological receptor. The prediction study was done with a set of three new compounds by using the PCA, HCA, SDA and KNN methods and two of them were predicted as active against T. cruzi .