A structure-activity study of synthesized sulfonamide derivatives on Human Carbonic Anhydrase II

Carbonic anhydrase isozymes distribute in almost all tissues. In mammals, these zinc containing family of enzymes (CAs, EC 4.2.1.1) are divided into at least 14 different isoforms. All the isoforms have similar tertiary structure folding, including a 10-stranded β-sheet as the principal secondary structure core. Tissue localization of this enzyme is in membrane, mitochondria and cytosol. Carbonic Anhydrase is mostly known as a pH-regulating enzyme which catalyzes reversible hydration of carbon dioxide in most tissues. Sulfonamides have the formula RSO2NH2 and are the most important compounds of CA inhibitors. These group of inhibitors are used to a large extent in clinical application for more than five decades as diuretics, ant glaucoma, and antidiabetic factors. Study of Changes in activity and structure upon interaction with inhibitors reveals details about mechanism of action, and associated with several disorders such as diabetes, glaucoma, etc. The catalytic activity and inhibition manner of these enzymes are being understood, and this may be resulted in designing new potent drugs. In this study, kinetic assay along with structural changes of some novel sulfonamide derivatives on human carbonic anhydrase II was monitored with UV-visible, CD and fluorescence techniques. Lineweaver-Burk plots showed different patterns of competitive and non-competitive inhibition modes. Secondary structure analysis showed slight turning of alpha helix to beta sheet and random coil. Intrinsic fluorescence analysis revealed more changes in comparison to control parallel to increment of ligand concentration. In this stage, our findings showed that these ligands inhibited the enzyme efficient without any remarkable structural changes.