Chpater 19 Carbonic Anhydrases from Pathogens: Fungal Carbonic Anhydrases And Their Inhibitors as Potential Antifungal Agents.

The main classes of clinically used antimycotic agents inhibit the fungal growth interfering with the biosynthesis, stabilization and integrity of the cell membrane and wall of these microorganisms. Most of the available drugs are affected by the spreading phenomenon of the anti-microbial resistance, which might be overcome by the discovery of new drug targets and anti-fungals endowed with an alternative mechanism of action. A crucial physiological reaction for the survival of fungi, as well as for all living organism, is the CO2 hydration/dehydration reaction catalyzed by a superfamily of metalloenzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1) and classified into seven genetically distinct families (or classes), named α-, β-, γ-, δ-, ζ-, η-, and ɵ-CAs. These metalloenzymes are implicated in the maintenance of the suitable equilibrium of CO2, HCO3- and H+, which are essential for several biosynthethic pathways and energy metabolism in fungi. Many pathogenic such species need functional CAs for their survival or for manifesting their virulence in the host. They mainly express β-CA isoforms, although α-class fungal enzymes have also been identified. The present chapter depicts the scenario of the fungi in which CA isoforms have been described. Insights in the various fungal CAs molecular architecture are provided as well as a collection of the inhibition data with several classes of chemotypes reported to date against these enzymes.