Carbonic anhydrase inhibitors. Phenols incorporating 2- or 3-pyridyl-ethenylcarbonyl and tertiary amine moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase

A series of phenols incorporating tertiary amine and trans-pyridylethenyl-carbonyl moieties were assayed as inhibitors of the beta-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA. One of these compounds was a low nanomolar ScCA inhibitor, whereas the remaining ones inhibited the enzyme with K(I)s in the range of 23.5-95.4 nM. The off-target human (h) isoforms hCA I and hCA II were much less inhibited by these phenols, with K(I)s in the range of 0.78-23.5 mu M (hCA I) and 10.8-52.4 mu M (hCA II). The model organism S. cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged

PREPARING AND OPTIMIZING A NEWLY AFFINITY GEL FOR PURIFICATION OF CARBONIC ANHYDRASE ISOENZYMES

Human carbonic anhydrase isozymes have been purified from the hemolysate, directly by using the original affinity gel in chemical structure of Sepharose 4B-L-tyrosine- sulfathiazole. Different solution buffers were used for obtaining the purified CA isozymes from the affinity column. Most suitable elution buffers were determined for CA I and CA II isoenzymes pH 6.3, 25 mM Na2HPO4/1.0 M NaCl and pH 5.6, 0.1 M NaCH3COO / 0.5 M NaClO4 respectively. The purification values for CA I and CA II have been obtained as 635.71 and 666.71 folds with 28.41% and 46.19% yield respectively. The ionic strength and optimum pH values of the original affinity gel have been determined for each isozyme of CA. Maximum binding was achieved 0.3 ionic strength and pH 8.7 for both CA I and CA II. The single bands was indicated for each isoenzymes by SDS-polyacrylamide gel electrophoresis.TUBITAK with 2209-A - University Student Research Project Support ProgramTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)This work has been supported by TUBITAK with 2209-A - University Student Research Project Support Program.WOS:0005358394000532-s2.0-8509191455

Carbonic anhydrase inhibitors. Phenols incorporating 2- or 3-pyridyl-ethenylcarbonyl and tertiary amine moieties strongly inhibit Saccharomyces cerevisiae

A series of phenols incorporating tertiary amine and trans-pyridylethenyl-carbonyl moieties were assayed as inhibitors of the beta-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA. One of these compounds was a low nanomolar ScCA inhibitor, whereas the remaining ones inhibited the enzyme with K(I)s in the range of 23.5-95.4 nM. The off-target human (h) isoforms hCA I and hCA II were much less inhibited by these phenols, with K(I)s in the range of 0.78-23.5 mu M (hCA I) and 10.8-52.4 mu M (hCA II). The model organism S. cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged