Carbonic anhydrase inhibitory properties of novel sulfonamide derivatives of aminoindanes and aminotetralins

Abstract

Six sulfonamides derived from indanes and tetralines were synthesized. The human carbonic anhydrase isozymes hCA I and hCA II inhibition effects of the synthesized sulfonamides were determined. From these compounds, while N-(5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl) methane sulfonamide showed the most potent inhibitory effect against hCA I (K i ¼ 46 AE 5.4 mM, r 2 ¼ 0.978), N-(1,2,3,4-tetrahydronaphthalene-2-yl)methanesulfonamide was found to have the best inhibitory effect against hCA II (K i ¼ 94 AE 7.6 mM, r 2 ¼ 0.982).

Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII)

“…It was reported that phenolic compounds act as CAIs 62,67,70,71 by binding to CA in a diverse manner compared to the classical CAIs, which coordinate the Zn 2+ ion in the active site of the enzyme by substituting a water molecule or hydroxide ion for the fourth, non-protein ligand 67,72 . X-ray crystallography studies from Christianson's group showed the inhibitor to be anchored by means of its -OH moiety to the fourth Zn 2+ ligand by means of a hydrogen bond.…”

Synthesis of N-alkyl (aril)-tetra pyrimidine thiones and investigation of their human carbonic anhydrase I and II inhibitory effects

“…a-CAs are among the most effective catalysts known in nature. The a-CAs are present in vertebrates, algae, protozoa, and cytoplasm compartment of green plants, as well as in some bacteria [27][28][29][30][31][32] . In humans, a-CAs are diffused in different tissues including the blood, kidneys, gastrointestinal tract, reproductive tract, the nervous central system, eyes, skin, lungs, etc.…”

“…Both isoenzymes purities were controlled by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) according to Laemmli's method 67 . SDS-PAGE was widely used in biochemistry for separation of biological macromolecule including proteins and enzymes according to their electrophoretic mobility 29 . SDS-PAGE was applied after purification of hCA I, and II isoenzymes.…”

Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase

“…There are sixth main genetic families encoding classes of these enzymes: a-, b-, g-, d-, z-and Z-CAs. It was reported that a-CAs are normally monomers and rarely dimers; b-CAs are dimers, tetramers or octamers; g-CAs are trimers, whereas the d-and z-CAs are less well understood at this moment [26][27][28][29][30] . a-CAs are found in algae, vertebrates, bacteria and cytoplasm of green plants.…”