Some drugs inhibit in vitro hydratase and esterase activities of human carbonic anhydrase-I and II.
In this study, we determined the in vitro inhibitory effects of ceftriaxone sodium, imipenem and ornidazole on hydratase and esterase activities of human erythrocyte carbonic anhydrase-I and II isozymes (CA I and II). Human erythrocyte CAI and II isozymes were purified by Sepharose-4B L-tyrosine affinity chromatography column with a yield of 30% and 40%, a specific activity of 920 and 8,000 EU/mg protein, respectively. In the overall purification procedure, human carbonic anhydrase (hCA)-I and (hCA)-II were purified 104 and 900-fold, respectively. In order to determine the purity of the enzymes, SDS-PAGE was performed. Inhibitory effects of the drugs on hCA-I and hCA-II were determined by using colorimetric method for CO2-hydratase activity assay and spectrophotometric method for esterase activity assay. P-Nitrophenyl acetate was used as a substrate in the spectrophotometric esterase activity assay. The obtained IC50 values (inhibitor concentrations which cause 50% inhibition of in vitro enzyme activity) for esterase activity were 1.900, 0.008, 0.318 mM for hCA-I and 2.542, 0.0258, 0.343 mM for hCA-II for ceftriaxone sodium, imipenem and ornidazole, respectively. IC50 values for CO2-hydratase activity were 0.864, 0.00354, 0.131 mM for hCA-I and 1.118, 0.0214, 0.263 mM for hCA-II for ceftriaxone sodium, imipenem and ornidazole, respectively. In conclusion, ceftriaxone sodium, imipenem and ornidazole showed inhibitory effects on human erythrocte carbonic anhydrase-I and II isozyme activities under in vitro conditions.
Atatürk University, Faculty of Science and Arts, Department of Chemistry, 25240 Erzurum, Turkey.
Deniz
D
Ekinci
Sükrü
S
Beydemir
Zuhal
Z
Alim
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000737:chemistry; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002443:Ceftriaxone / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology; D004950:Esterases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D009950:Ornidazole / Q000494:pharmacology; D051381:Rats
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000981:Antiprotozoal Agents; D007527:Isoenzymes; D009950:Ornidazole; D015378:Imipenem; D002443:Ceftriaxone; D004950:Esterases; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II