Carbonic anhydrase inhibitors - Part 47: Quantum chemical quantitative structure-activity relationships for a group of sulfanilamide Schiff base inhibitors of carbonic anhydrase

A series of sulfanilamide Schiff base inhibitors of CA I and CA IT have been studied by the semi-empirical AM1 method. The charges on the atoms of the sulfonamide group, and the dipole moment, have been calculated by four methods: a standard vacuum calculation, a solution calculation by the COSMO method, a solution calculation with, in addition, the charges and dipole moments calculated by fitting to the calculated electrostatic potential, and a calculation by the older CNDO method. The data were subjected to a classical multiple regression analysis with care to avoid the possibility of chance correlation or collinearity. The ACE technique was also used to allow for nonlinearity. A number of statistically significant equations were derived, which were mostly consistent with previous studies. While the ESP-based charges gave the best equations, the improvement was not sufficient to convincingly exclude the other methods. This is the first study which evidenced by means of QSAR calculations isozyme-specific features of the two isozymes CA I and CA II, in their interaction with sulfonamide inhibitors. (C) Elsevier, Paris.