A quantitative structure–activity relationship study on some aromatic/heterocyclic sulfonamides and their charged derivatives acting as carbonic anhydrase inhibitors

Abstract

A quantitative structure–activity relationship (QSAR) study is made on a series of aromatic/heterocyclic sulfonamides and their charged derivatives acting as carbonic anhydrase (CA) inhibitors. These compounds were studied by Scozzafava et al. (J. Med. Chem. 2000; 43: 292) for the selective inhibition of CAs—sulfonamides generally do not discriminate between different CA isozymes and hence exhibit many undesirable side effects when used as drugs against a particular disease. In this communication, an attempt has been made to investigate the physicochemical and structural properties that can make them selective for a given CA isozyme. Based on in vitro data reported by Scozzafava et al. against two cytosolic isozymes and one membrane-bound isozyme, the QSAR study has shown that uncharged compounds cannot be made selective for cytosolic or membrane-bound isozyme since in both the cases the compounds appear to follow the same mechanism of inhibition. However, for the charged compounds the polarizability of the molecule seems to greatly favor the inhibition of the membrane-bound enzyme, and hence they can be made selective for this enzyme by enhancing their polarizability, which is found to play no role in the inhibition of cytosolic enzymes.