The investigation of the carbonic anhydrase inhibition effects of thiadiazole derivatives on human carbonic anhydrase enzyme

Carbonic anhydrases (E.C. 4.2.1.1.) are family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide in a two-stop reaction to yield bicarbonate and proton. The isoenzymes of human eye are CA-I, CAII and CA-IV. Carbonic anhydrase inhibitors, which reduce aqueous production with a corresponding decrease in intraocular pressure (IOP), have been used as ocular hypotensive agents for the treatment of glaucoma.In this study, new carbonic anhydrase inhibitors?s effects on carbonic anhydrase enzyme as candidates for treatment of glaucoma were investigated.First, carbonic anhydrase enzymes from human erythrocyte were purifed using affinity gel and all of the investigations were carried out with these enzymes.Later, inhibition effects of these new compounds (1, 2, 3 ) on human carbonic anhydrase enzymes (HCA I and HCA II) were investigated in vitro. In the studies, it was taken advantage of hydrates and esterase activites for determining of carbonic anhydrase activitates. It was observed that compounds (1, 2, 3) showed inhibition effect on HCA hydratase and esterase activity. I50 values were determined by drawing % activity-[I] graphs for drugs showing inhibition effects. For CO2-hydratase activity of compound (1), (2), (3) inhibition effect ranged from 0,080 to 0,800 ? M for HCA I and 0,053 to 0,480 ? M with I50 for HCA II (molarity of inhibitor producing a %50 inhibition of CA activity). As for esterase activity of p-nitrophenyl acetate, compounds (1), (2), (3) had inhibition ranging from 0,097 to 3,798 ? M for HCA I and 0,046 to 0,361 ? M for HCA II with I50.Key Words: Glaucoma, I50 Values, Carbonic Anhydrase, Sulfonamides