QSAR study of the calcium channel antagonist activity of some recently synthesized dihydropyridine derivatives. An application of genetic algorithm for variable selection in MLR and PLS methods

Quantitative structure–activity relationship (QSAR) analysis has been directed to a series of recently synthesized nifedipine analogues containing the nitroimidazolyl group at the C-4 position and different ester substituents at C-3 and C-5 positions of the 1,4-dihydropyridine (DHP) ring. Modeling of the calcium channel antagonist activity of these compounds as a function of the theoretically derived descriptors was established by multiple linear regression (MLR) and partial least squares (PLS) regression. The genetic algorithm (GA) was used for the selection of the variables that resulted in the best-fitted models. Appropriate models with low standard errors and high correlation coefficients were obtained. Topology, hydrophobicity and surface area examples of the descriptors affected by the binding of dihydropyridine to the receptor. A comparison of the two regression methods used showed that PLS has a better prediction ability than MLR.