Carbonic Anhydrase Inhibitors. Metal Complexes of 5-(2-Chlorophenyl)-1, 3, 4-Thiadiazole-2-Sulfonamide with Topical Intraocular Pressure Lowering Properties: The Influence of Metal Ions Upon the Pharmacological Activity |
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Authors: | Fabrizio Briganti Silvia Tilli Giovanna Mincione Francesco Mincione Luca Menabuoni |
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Affiliation: | 1. Laboratorio di Chimica Inorganica e Bioinorganica, Università degli Studi, Via Gino Capponi 7, I-50121, Firenze, Italia;2. Institute of Ophthalmology, Università degli Studi, Vide Morgagni 85, 1-50134, Firenze, Italia;3. Ospedale Sun Giovanni di Dio, S.O. Oculistica, Via Torregalli 3, I-50123, Firenze, Italia |
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Abstract: | Metal complexes of a sulfonamide possessing strong carbonic anhydrase (CA) inhibitory properties, 5-(2-chlorophenyl)-1, 3, 4-thiadiazole-2-sulfonamide (chlorazolamide) have been obtained from the sodium salt of the sulfonamide and the following metal ions: Mg(II), Zn(II), Mn(II), Cu(II), Co(II), Ni(II), Be(II), Cd(II), Pb(II), AI(III), Fe(III) and La(III). The original sulfonamide and its complexes were assayed for the in vitro inhibition of three CA isozymes, CA I, II, and IV, some of which play a critical role in ocular fluid secretion. All these compounds (the sulfonamide and its metal complexes) behaved as powerful inhibitors against the three investigated isozymes. The parent sulfonamide possessed an extremely weak topical pressure lowering effect when administered as a 1-2% suspension into the rabbit eye, but some of its metal complexes, such as the Mg(II), Zn(II), Mn(II) and Cu(II) derivatives, lower intraocular pressure (IOP) in experimental animals very well. Ex vivo data showed a 99.5-99.9% CA II inhibition in ocular fluids and tissues of rabbits treated with these agents, proving that the observed IOP lowering is due to CA inhibition. The influence of the different metal ions upon the efficiency of the obtained complexes as pressure lowering drugs are discussed, leading to the possibility of designing more selective; potent pharmacological agents from this class |
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Keywords: | Topical sulfonamlde Chlorazolamide Carbonic anhydrase Metal complex Intraocular pressure lowering Antiglaucoma drug |
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