Potent and selective carbonic anhydrase inhibition activities of pyrazolones bearing benzenesulfonamides

This research introduces a series of fourteen 4-aryl-hydrazonopyrazolone sulfonamide derivatives, denoted as 3 (a-g) and 4(a-g), which encompass various aromatic substitutions. The aim was to assess the inhibitory potential of these compounds against four significant isoforms, including the cytosolic isoforms hCA I and II, as well as the tumor-associated membrane-bound isoforms hCA IX and XII. Most of the tested compounds exhibited substantial inhibition against the tumor-associated isoform hCA IX, with Ki values spanning from 1.1 to 158.2 nM. Notably, compounds 3e and 3g showed particularly strong inhibitory activity against the tumor-associated membranebound isoforms, hCA IX and XII, while maintaining a high selectivity ratio over cytosolic off-target isoforms hCA I and II. This selectivity is vital due to the potential of hCA IX and hCA XII as drug targets for hypoxic tumors. In an effort to create novel analogs that exhibit enhanced carbonic anhydrase inhibitory activity and specificity, we investigated the structure-activity relationships of these compounds and provided a concise interpretation of our findings. Consequently, these compounds merit consideration for subsequent medicinal and pharmacological research, holding potential for developing novel therapeutic agents targeting specific isoforms in hypoxic tumors.

Automated summary

This research introduces a series of compounds that exhibit significant inhibitory activity against tumor-associated isoforms of carbonic anhydrase, with certain selectivity. Investigating the structure-activity relationships of these compounds could provide insights for the development of novel therapeutic agents targeting hypoxic tumors.