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

We investigated the inhibition of five physiologically relevant CA isoforms with photochromic cis-1,2-α-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 (KIs 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 (KIs of 13–18 nM). hCA IX was moderately inhibited by these compounds (KIs of 9–376 nM) whereas hCA XII and XIV were less susceptible to inhibition (KIs of 1.12–16.7 μM).

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