Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides.

Anthony Bertucci, Alessio Innocenti, Didier Zoccola, Andrea Scozzafava, Sylvie Tambutté, Claudiu T Supuran

Centre Scientifique de Monaco, Avenue Saint-Martin, MC-98000 Principality of Monaco, Monaco.

Bioorganic & medicinal chemistry 2009 Jul 15

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The inhibition of a newly cloned coral carbonic anhydrase (CA, EC 4.2.1.1) has been investigated with a series of sulfonamides, including some clinically used derivatives (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and sulpiride, or indisulam, a compound in clinical development as antitumor drug), as well as the sulfamate antiepileptic topiramate. Some simple amino-/hydrazine-/hydroxy-substituted aromatic/heterocyclic sulfonamides have also been included in the study. All types of activity have been detected, with low potency inhibitors (K(I)s in the range of 163-770nM), or with medium potency inhibitors (K(I)s in the range of 75.1-105nM), whereas ethoxzolamide, several clinically used sulfonamides and heterocyclic compounds showed stronger potency, with K(I)s in the range of 16-48.2nM. These inhibitors may be useful to better understand the physiological role of the Stylophora pistillata CA (STPCA) in corals and its involvement in biomineralisation in this era of global warming.

Citation

Anthony Bertucci, Alessio Innocenti, Didier Zoccola, Andrea Scozzafava, Sylvie Tambutté, Claudiu T Supuran. Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorganic & medicinal chemistry. 2009 Jul 15;17(14):5054-8