Carbonic anhydrase inhibitors: synthesis of sulfonamides incorporating dtpa tails and of their zinc complexes with powerful topical antiglaucoma properties.

Article Details

Citation

Scozzafava A, Menabuoni L, Mincione F, Mincione G, Supuran CT

Carbonic anhydrase inhibitors: synthesis of sulfonamides incorporating dtpa tails and of their zinc complexes with powerful topical antiglaucoma properties.

Bioorg Med Chem Lett. 2001 Feb 26;11(4):575-82.

PubMed ID
11229775 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
4-(2-AMINOETHYL)BENZENESULFONAMIDECarbonic anhydrase 2Ki (nM)160N/AN/ADetails
6-HYDROXY-1,3-BENZOTHIAZOLE-2-SULFONAMIDECarbonic anhydrase 2Ki (nM)8N/AN/ADetails
AcetazolamideCarbonic anhydrase 1Ki (nM)900N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
AcetazolamideCarbonic anhydrase 4Ki (nM)220N/AN/ADetails
DorzolamideCarbonic anhydrase 1Ki (nM)>50000N/AN/ADetails
DorzolamideCarbonic anhydrase 2Ki (nM)9N/AN/ADetails
DorzolamideCarbonic anhydrase 4Ki (nM)43N/AN/ADetails