Abstract
Metal complexes of heterocyclic sulfonamides possessing carbonic anhydrase (CA) inhibitory properties were recently shown to be useful as intraocular pressure (IOP) lowering agents in experimental animals, and might be developed as a novel class of antiglaucoma drugs. Here we report the synthesis of a heterocyclic sulfonamide CA inhibitor and of the metal complexes containing main group metal ions, such as Be(II), Mg(II), Al(III), Zn(II), Cd(II) and Hg(II) and the new sulfonamide as well as 5-amino-1,3,4-thiadiazole-2-sulfonamide as ligands. The new complexes were characterized by standard physico-chemical procedures, and assayed as inhibitors of three CA isozymes, CA I, II and IV. Some of them (but not the parent sulfonamides) strongly lowered IOP in rabbits when administered as a 2% solution into the eye.
Highlights
Sulfonamides possessing carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties [2] such as acetazolamide 1, methazolamide 2, ethoxzolamide 3 and dichlorophenamide 4 have been used for more than years as pressure lowering systemic drugs in the treatment of open-angle glaucoma [3,4]. Their effect is due to inhibition of at least two CA isozymes present within cilliary processes of the eye, ie, CA II and CA IV, which is followed by lowered bicarbonate formation and reduction of aqueous humor secretion [5-7]
We proved [25, 26] that some metal complexes of heterocyclic sulfonamides act as very powerful such agents when administered as diluted solutions directly into the eye of experimental animals, and would offer the possibility of developing such totally novel drugs
Reaction of 5-amino-l,3,4-thiadiazole-2-sulfonamide 6 [19b] with chloroacteyl chloride in the presence of pyridine afforded 5-(chloroacetamido)-l,3,4-thiadiazole-2-sulfonamide 7, by the procedure already reported by Young et al [34] (Scheme 1)
Summary
Universit& degli Studi, Dipartimento di Chimica, Laboratorio di Chimica Inorganica e Bioinorganica, Via Gino Capponi 7, 1-50121, Florence, Italy.
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