Carbonic anhydrase inhibitors: two-prong versus mono-prong inhibitors of isoforms I, II, IX, and XII exemplified by photochromic cis-1,2-alpha-dithienylethene derivatives

Abstract

We investigated the inhibition of five physiologically relevant CA isoforms with photochromic cis-1,2-alpha-dithienylethene-based compounds incorporating either a benzenesulfonamide and Cu(II)-iminodiacetic acid (IDA)-, bis-benzenesulfonamide-, bis-Cu(II)-IDA-, and bis-ethyleneglycol-methyl ether moieties, in both their open- and closed-ring forms. For hCA I the best inhibitors were the mono-prong bis-sulfonamide and the bis-Cu-IDA complexes (K(I)s of 2-3 nM) in their open form. For hCA II, best inhibitors were the open and closed forms of the mono-prong bis-sulfonamide (K(I)s of 13-18 nM). hCA IX was moderately inhibited by these compounds (K(I)s of 9-376 nM) whereas hCA XII and XIV were less susceptible to inhibition (K(I)s of 1.12-16.7 microM).