Abstracto

Therapeutic applications of the carbonic anhydrase inhibitors

Claudiu T Supuran

Inhibitors of the zinc enzyme carbonic anhydrase (CA) targeting different isozymes among the 15 presently reported in humans have various therapeutic applications. These enzymes are efficient catalysts for the hydration of carbon dioxide to bicarbonate and protons, playing crucial physiological/pathological roles related to acid–base homeostasis, secretion of electrolytes, transport of ions, biosynthetic reactions and tumorigenesis. Many CA inhibitors have been reported as antiglaucoma, anticancer and antiobesity agents, or for the management of a variety of neurological disorders, including epilepsy and altitude disease. Furthermore, some CA isozymes appear to be valuable markers of tumor progression in a variety of tissues/organs. Various CAs present in pathogens such as Plasmodium falciparum, Helicobacter pylori, Mycobacterium tuberculosis, Candida albicans and Cryptococcus neoformans, have started to also be investigated recently as drug targets. Recent progress in all these areas, as well as in the characterization of new such enzymes isolated in many other organisms/tissues, in addition to their detailed catalytic/inhibition mechanisms, are reviewed herein, together with the therapeutic use of these enzyme inhibitors and drug-design studies for obtaining such new-generation derivatives with improved activity.