Drug Design Studies of Carbonic Anhydrase Activators

Polyamines and α-Carbonic Anhydrases

“…The typical structural features associated with CAAs are a proper fitting of the ligand within the enzymatic cleft as well as the presence on it of protonatable moieties with pKa values spanning between 6.5 and 8.0 [16]. Thus, it is expected that the polyamines act as CAAs.…”

“…Thus, the enzyme is catalytically more efficient in the hydration of the natural ligand carbon dioxide [16][17][18][19][20][21][22][23].…”

“…The classical CA activators (CAAs) include biogenic amines such as hystamine or amino acids of the type reported below (Figure 3) [16][17][18][19][20]. From the mechanistic viewpoint, the CAAs act at the last step of the CA catalytic cycle (conversion of D to A in Scheme 2), which is also the rate-determining one.…”

“…The classical CA activators (CAAs) include biogenic amines such as hystamine or amino acids of the type reported below (Figure 3) [16][17][18][19][20]. to a multi-targeting effect, such as gene and ionic channel deregulations, destabilization of biological macromolecules (i.e., DNA and RNA), as well as induced alteration of the functionality of some cellular organelles.…”

Synthesis and characterization of phenolic Mannich bases and effects of these compounds on human carbonic anhydrase isozymes I and II

“…Since CA inhibitors have been shown to reduce IOP exclusively by lowering the aqueous humour flow and these compounds have been used for the treatment of glaucoma for years 11,12 . The rate-determining step for the CO 2 hydration reaction catalyzed by CAs is the proton transfer reaction from the water bound to the Zn(II) ion to the reaction medium, with generation of the zinc hydroxide species of the enzyme [13][14][15][16][17][18][19][20] . Several anions behave as inhibitors for the CO 2 hydration reaction 21,22 and coordinate directly to Zn(II) ion.…”