Inhibitory effects of sulfenimides on human and bovine carbonic anhydrase enzymes

A series of sulfenimide derivatives (1a-i) were investigated as inhibitors of human (hCA-I, hCA-II) and bovine (bCA) carbonic anhydrase enzymes. The compounds were synthesised by the reaction of substituted thiophenols with phthalimide by means of an effective, simple and eco-friendly method and the structures were confirmed by IR, H-1 NMR, C-13 NMR, MS and elemental analysis. All derivatives except for the methyl derivative (1b) exhibited effective inhibitory action at low micromolar concentrations on human isoforms, but only four derivatives (1e, 1f, 1h, 1i) inhibited the bovine enzyme. The bromo derivative (1f) was found to be strongest inhibitor of all three enzymes with KI values of 0.023, 0.044 and 20.57 mu M for hCA-I, hCA-II and bCA, respectively. Results of our study will make valuable contributions to carbonic anhydrase inhibition studies for further investigations since inhibitors of this enzyme are important molecules for medicinal chemistry.

Automated summary

A series of sulfenimide derivatives were synthesized via an efficient, simple and eco-friendly method and were found to be effective inhibitors of human and bovine carbonic anhydrase enzymes. The structures of the derivatives were confirmed by various techniques. These compounds showed strong inhibitory activity at low micromolar concentrations on human isoforms, while only four derivatives inhibited the bovine enzyme. One of the derivatives, the bromo derivative, was found to be the strongest inhibitor for all three enzymes. This study provides valuable contributions to further investigations on carbonic anhydrase inhibition in medicinal chemistry.