Carbonic anhydrases: novel therapeutic applications for inhibitors and activators

Carbonic anhydrases (CAs) are a large family of ubiquitous metalloenzymes that are involved in many physiological and pathological processes. Traditionally, CA inhibition has been clinically applied in the development of diuretic and antiglaucoma agents. Supuran discusses the emerging potential for inhibitors or activators of CAs to treat a wide range of other disorders, including obesity, cancer, osteoporosis, bacterial and fungal infections, as well as Alzheimer's disease. Carbonic anhydrases (CAs), a group of ubiquitously expressed metalloenzymes, are involved in numerous physiological and pathological processes, including gluconeogenesis, lipogenesis, ureagenesis, tumorigenicity and the growth and virulence of various pathogens. In addition to the established role of CA inhibitors (CAIs) as diuretics and antiglaucoma drugs, it has recently emerged that CAIs could have potential as novel anti-obesity, anticancer and anti-infective drugs. Furthermore, recent studies suggest that CA activation may provide a novel therapy for Alzheimer's disease. This article discusses the biological rationale for the novel uses of inhibitors or activators of CA activity in multiple diseases, and highlights progress in the development of specific modulators of the relevant CA isoforms, some of which are now being evaluated in clinical trials.