Evaluation of some thiophene-based sulfonamides as potent inhibitors of carbonic anhydrase I and II isoenzymes isolated from human erythrocytes by kinetic and molecular modelling studies.

Thiophene(s) are an important group in therapeutic applications, and sulfonamides are the most important class of carbonic anhydrase (CA) inhibitors. In this study, inhibition effects of some thiophene-based sulfonamides on human erythrocytes carbonic anhydrase I and II isoenzymes (hCA-I and hCA-II) were investigated. Thiophene-based sulfonamides used in this study showed potent inhibition effect on both isoenzymes at very small concentrations. We report on the purification of the carbonic anhydrase I and II isoenzymes (hCA-I and hCA-II) using affinity chromatography method. The inhibition effect of the thiophene-based sulfonamides was determined by IC50 and Ki parameters. A molecular docking study was performed for each molecule. Thiophene-based sulfonamides showed IC50 values of in the range of 69 nM to 70 µM against hCA-I, 23.4 nM to 1.405 µM against hCA-II. Ki values were in the range of 66.49 ± 17.15 nM to 234.99 ± 15.44 µM against hCA-I, 74.88 ± 20.65 nM to 38.04 ± 12.97 µM against hCA-II. Thiophene-based sulfonamides studied in this research showed noncompetitive inhibitory properties on both isoenzymes. To elucidate the mechanism of inhibition, a molecular docking study was performed for molecules 1 and 4 exhibiting a strong inhibitory effect on hCA-I and hCA-II. The compounds inhibit the enzymes by interacting out of catalytic active site. The sulfonamide and thiophene moiety played a significant role in the inhibition of the enzymes. We hope that this study will contribute to the design of novel thiophene-based sulfonamide derived therapeutic agents that may be carbonic anhydrase inhibitors in inhibitor design studies.