Synthesis and human/bacterial carbonic anhydrase inhibition with a series of sulfonamides incorporating phthalimido moieties

A series of sulfonamides was obtained by reacting substituted-2-(1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxamido)benzoic acids with aromatic sulfonamides incorporating primary amino moieties. The new compounds were investigated as inhibitor of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I and II, and the alpha- and beta-class CAs from the pathogenic bacterium Vibrio cholerae, VchCA alpha, and VhcCA beta. hCA I was effectively inhibited by the new sulfonamides, with inhibition constants in the range of 4.9-96.0 nM. hCA II also showed high affinity for these compounds (K(I)s of 2.1-22.3 nM), whereas the two bacterial enzymes were less effectively inhibited, with K(I)s of 281-3192 nM for VchCA alpha, and 5.40-9.26 mu M for VhcCA beta. As the physiological function hCA I is poorly understood, and it was recently shown to be involved in the pathogenesis of cerebral malaria and amyotrophic lateral sclerosis, selective and effective inhibitors may be useful as tools or drugs for better understanding this abundant isoform. (C) 2017 Elsevier Ltd. All rights reserved.