Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits.
Article Details
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Winum JY, Casini A, Mincione F, Starnotti M, Montero JL, Scozzafava A, Supuran CT
Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits.
Bioorg Med Chem Lett. 2004 Jan 5;14(1):225-9.
- PubMed ID
- 14684332 [ View in PubMed]
- Abstract
A series of N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines was prepared by reaction of sulfanilamide with different monosaccharides in the presence of ammonium chloride. The new compounds were investigated for inhibition of the metallo-enzyme carbonic anhydrase (CA, EC 4.2.1.1), involved in aqueous humor secretion within the mammalian eye. Isozymes CA I and CA II were strongly inhibited by some of these compounds, which showed inhibition constants in the range of 510-1200 nM against CA I and 10-25 nM against CA II, similarly to clinically used sulfonamides, such as acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide. The presence of sugar moieties in these molecules induced an enhanced water solubility as compared to other sulfonamides. In hypertensive rabbits (a widely used animal model of glaucoma), two of the new compounds showed strong and long-lasting intraocular pressure (IOP) lowering, being more effective than dorzolamide and brinzolamide, the two clinically used, topically acting antiglaucoma sulfonamides with CA inhibitory properties.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Brinzolamide Carbonic anhydrase 1 Protein Humans UnknownInhibitorDetails Brinzolamide Carbonic anhydrase 2 Protein Humans YesInhibitorDetails Diclofenamide Carbonic anhydrase 1 Protein Humans YesInhibitorDetails Methazolamide Carbonic anhydrase 1 Protein Humans YesInhibitorDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 900 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Brinzolamide Carbonic anhydrase 2 Ki (nM) 3 N/A N/A Details Diclofenamide Carbonic anhydrase 1 Ki (nM) 1200 N/A N/A Details Diclofenamide Carbonic anhydrase 2 Ki (nM) 38 N/A N/A Details Dorzolamide Carbonic anhydrase 1 Ki (nM) >50000 N/A N/A Details Dorzolamide Carbonic anhydrase 2 Ki (nM) 9 N/A N/A Details