Inhibition of carbonic anhydrase isozymes I, II and IX with benzenesulfonamides containing an organometallic moiety.
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A novel series of benzenesulfonamides that contain ferrocenyl or ruthenocenyl moieties were synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant carbonic anhydrase (CA) isozymes: hCA I, II and tumour-associated IX (h = human). This manuscript describes the regioselective synthesis of both the 1,4- and 1,5-disubstituted-1,2,3-triazole benzenesulfonamides from ethnylmetallocene substrates This is the first report describing the covalent attachment of organometallic moieties to the arylsulfonamide (ArSO2NH2) CA recognition pharmacophore. At hCA I these metallocene derivatives were either nanomolar or low micromolar inhibitors, while against hCA II and IX inhibition in the range of 9.7-80 nM and 10.3-85 nM, respectively was observed. The ruthenocenyl derivatives gave superior CA inhibition compared to the ferrocenyl compounds across all three CA isozymes. These compounds constitute a new organometallic class of CA inhibitors with promising biological activity.
Bioorganic & Medicinal Chemistry Letters