Discovery of novel drugs for Chagas disease: is carbonic anhydrase a target for antiprotozoal drugs?

Inhibition studies with simple and complex (in)organic anions of the γ-carbonic anhydrase from Mammaliicoccus (Staphylococcus) sciuri, MscCAγ

“…By efficiently catalysing the hydration of CO 2 to bicarbonate and protons, these enzymes participate in many crucial physiologic processes, such as pH regulation 1–4 , metabolism (as they are involved in several biosynthetic pathways) 5 , photosynthesis (in plants and cyanobacteria) 6 , electrolyte secretion (in vertebrates) 7 , respiration and CO 2 /bicarbonate homeostasis 8 , just to mention the essential ones. Bacteria encode for at least 4 CA classes (α-, β-, γ- and ι-CAs) 2 , 4 and in many pathogenic ones (but also in fungi or protozoans) the CAs are also involved in virulence, acclimation in specific tissues/organs and pathogen survival/fitness in environments possessing highly variable pH, bicarbonate and CO 2 levels 2 , 9 . Thus, recently, inhibition of bacterial CAs started to be considered as a valid approach for obtaining antibiotics with a novel mechanism of action 2 , 10 , 11 , and at least for Helicobacter pylori 12 , Neisseria gonorrhoeae 11 , 13 and vancomycin-resistant Enterococci 14 , detailed in vitro , in vivo and animal model proof-of-principle studies provided the experimental evidence that the approach is feasible and provides a powerful antibacterial effect 2 , 10–14 .…”