Discovery of the first-in-class potent and isoform-selective human carbonic anhydrase III inhibitors.

ABSTRACT: Considering the unrecognised physio-pathological role of human carbonic anhydrase III (hCA III), a structure-based drug design was set up to identify the first-in-class potent and selective inhibitors of this neglected isoform. hCA III targeting was planned considering a unique feature of its active site among the other hCA isoforms, i.e. the Leu198/Phe198 substitution which interferes with the binding of aromatic/heterocyclic sulfonamides and other inhibitors. Thus, new aliphatic primary sulfonamides possessing long and flexible (CH₂)_nSO₂NH₂ moieties were designed to coordinate the zinc(II) ion, bypassing the bulky Phe198 residue. They incorporate 1,2,3-triazole linkers which connect the tail moieties to the sulfonamide head, enhancing th

SUBMITTER: Giovannuzzi S 

PROVIDER: S-EPMC10128460 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature