Searching for novel carbonic anhydrase inhibitors: from virtual screening to the lab bench

Carbonic Anhydrases (CAs) are zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate both in prokaryotes and eukaryotes. In this context, Computer Aided Drug Design strategies have emerged as powerful tools in the modern drug discovery paradigm. In particular, using ligand- and pharmacophore-based virtual screening approaches, we identified novel chemical entities with original chemotypes, that showed an interesting and selective inhibitory activity in nanomolar/low micromolar range toward CA I and CAII, isoforms.Herein, we present the hit-to-lead optimization process for these prototypes.