Carbonic anhydrase activators. 3: structure-activity correlations for a series of isozyme II activators

A quantitative structure-activity relationship for some arylalkylamine and arylalkylamino acid activators of carbonic anhydrase, of diverse chemical structure, is presented. A number of descriptors were calculated by the complete neglect of differential overlap (CNDO/2) method, and related to biological activity by regression analysis and partial least squares. Both charge, in the form of the charge of the most highly charged atom in the molecule, and size, in the form of the smallest dimensions of the molecule, are shown to be important descriptors. It is shown that molecules bearing highly charged oxygen or nitrogen atoms tend to have high activity, and that the enzyme can accommodate molecules of only a limited size.