Purification of carbonic anhydrase from dog erythrocytes and investigation of in vitro inhibition by various compounds.
The enzyme carbonic anhydrase (E.C. 4.2.1.1) has a stimulatory effect on glaucoma, an eye disease that has a risk to dogs, which are models for the human eye disease, that is similar to that in humans. In this study, some sulfonamide derivatives, 2-(3-cyclohexene-1-carbamido)-1,3,4-thiadiazole-5-sulfonamide (CCTS), 4-(3-cyclohexene-1-carbamido) methyl-benzenesulfonamide (CCBS), 2-(9-octadecenoylamido)-1,3,4-thiadiazole-5-sulfonamide (ODTS), 2-(4,7,10-trioxa-tetradecanoylamido)-1,3,4-thiadiazole-5-sulfonamide (TDTS), and 2-(8-methoxycoumarine-3-carbamido)-1,3,4-thiadiazole-5-sulfonamide (MCTS), as well as some anionic compounds (perchlorate and chloride) and existing medicines (dorzolamide-HCl, gentamicine sulphate, tropicamide, and procaine-HCl) were assayed for their inhibition of dog carbonic anhydrase (dCA), which was purified from erythrocytes on an affinity gel of L-tyrosine-sulfonamide-Sepharose 4B. ODTS showed the highest potency amongst the synthetic compounds with IC50 value 1.18 x 10(-5) M. Amongst the medicines tested, only dorzolamide showed inhibition with IC50 value 5.05 x 10(-4) M. Procaine and tropicamide actually showed an activatory effect, whereas gentamicine sulfate had no significant effect. The inhibitory effects of anionic compounds such as perchlorate and chloride were also investigated; whereas perchlorate showed inhibition, chloride did not.
Bayram
Turan
T
Balikesir University, Science & Art Faculty, Department of Chemistry, Cagis Yerleskesi, Kampus, 10100, Balikesir, Turkey.
Arslan
Oktay
O
Ugras
Halil Ibrahim
HI
Cakir
Umit
U
Ozensoy
Ozen
O
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000302:isolation & purification* / Q000378:metabolism*; D002846:Chromatography, Affinity; D004285:Dogs; D004912:Erythrocytes / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure
D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases