Quantitative structure-activity relationships employing independent quantum chemical indices.

Derivation of quantitative structure-activity relationships between pharmacological potencies and the electronic structure of molecules may often result in chance correlations, because of the large number of quantum chemical indices. Interrelationships between the parameters complicate the interpretation of the results. Quantum chemical indices of benzylamines, tetracyclines, and 1,4-benzodiazepines were transformed into mutually independent components using principal component analysis. The number of essential components was 3, 4, and 3, respectively. The computational efforts needed to develop multivariate linear regression equations between these components and the pharmacological activities were reduced, since the regression coefficients were not affected by the inclusion of new parameters. In each example, the first component, which accounted for the highest part of the total sample variance in the electronic structure, was the most important one in determining pharmacological activity. It seems that besides the electrostatic forces, charge transfer also affected the inhibitory potencies of benzylamines.