Carbonic anhydrase inhibitors: synthesis of sulfonamides incorporating dtpa tails and of their zinc complexes with powerful topical antiglaucoma properties.
Reaction of diethylenetriamino pentaacetic acid (dtpa) dianhydride with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded bis-sulfonamides containing metal-complexing, polyamino-polycarboxylic acid moieties in their molecule. The corresponding mono-sulfonamide derivatives of dtpa were also obtained by an alternative method, from the free acid. Zn(II) complexes of these new sulfonamides were then prepared. Many of these derivatives showed nanomolar affinity towards isozymes I, II and IV of carbonic anhydrase (CA). Some of the best inhibitors were applied as 2% water solutions/suspensions into the eye of normotensive or glaucomatous albino rabbits, when strong and long-lasting intraocular pressure (IOP) lowering was observed.
Università degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Firenze, Italy.
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D000287:Administration, Topical; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005901:Glaucoma / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects; D004369:Pentetic Acid; D021281:Quantitative Structure-Activity Relationship; D011817:Rabbits; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D015032:Zinc
D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D004369:Pentetic Acid; D015032:Zinc