A series of furazan and furoxan sulfonamides were prepared and studied for their ability to inhibit human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX, and hCA XII. The simple methyl substituted products 3–5 were potent inhibitors. Differing structural modifications of these leads had differing effects on potency and selectivity. In particular, products in which the sulfonamide group is separated from the hetero ring by a phenylene bridge retained high potency only on the hCA XII isoform. The sulfonamides 3–5 exerted intraocular pressure (IOP) lowering effects in vivo in hypertensive rabbits more efficiently than dorzolamide. Some other products (39–42), although less effective in vitro hCA II/XII inhibitors, also effectively lowered IOP in two different animal models of glaucoma.

Furazan and furoxan sulfonamides are strong α-carbonic anhydrase inhibitors and potential antiglaucoma agents

CHEGAEV, Konstantin;LAZZARATO, Loretta;BOSCHI, Donatella;BLANGETTI, Marco;FRUTTERO, Roberta;
2014

Abstract

A series of furazan and furoxan sulfonamides were prepared and studied for their ability to inhibit human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX, and hCA XII. The simple methyl substituted products 3–5 were potent inhibitors. Differing structural modifications of these leads had differing effects on potency and selectivity. In particular, products in which the sulfonamide group is separated from the hetero ring by a phenylene bridge retained high potency only on the hCA XII isoform. The sulfonamides 3–5 exerted intraocular pressure (IOP) lowering effects in vivo in hypertensive rabbits more efficiently than dorzolamide. Some other products (39–42), although less effective in vitro hCA II/XII inhibitors, also effectively lowered IOP in two different animal models of glaucoma.
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http://www.sciencedirect.com/science/journal/09680896
Carbonic anhydrase; pharmacology/therapeutic use, Sulfonamides; IOP; Glaucoma
Konstantin Chegaev; Loretta Lazzarato; Yasinalli Tamboli; Donatella Boschi; Marco Blangetti; Andrea Scozzafava; Fabrizio Carta; Emanuela Masini; Roberta Fruttero; Claudiu T. Supuran; Alberto Gasco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/147999
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