Carbonic anhydrase activators

Abstract

Mammalian carbonic anhydrases (CAs; EC 4.2.1.1) of which 16 isoforms are known, are involved in important physiological functions. Their inhibition is exploited pharmacologically for the treatment of many diseases (glaucoma, edema, epilepsy, obesity, hypoxic tumors, neuropathic pain, etc.) but the activators were less investigated till recently. A review on the CA activation is presented, with the activation mechanism, drug design approaches of activators and comparison of the various isoforms activation profiles being discussed. Some CAs, which are abundant in the brain, were recently demonstrated to be activatable by drug-like compounds, affording the possibility to design agents that enhance cognition, with potential therapeutic applications in aging and neurodegenerative diseases as well as tissue engineering.

Keywords: activator; amine; amino acid; carbonic anhydrase; cognition enhancement; proton transfer.