Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform.

Article Details

Citation

Maryanoff BE, McComsey DF, Costanzo MJ, Hochman C, Smith-Swintosky V, Shank RP

Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform.

J Med Chem. 2005 Mar 24;48(6):1941-7.

PubMed ID
15771438 [ View in PubMed
]
Abstract

This paper examines the relative effectiveness of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II (CA-II). Topiramate (1) and its sulfamide analogue 4, and 4,5-cyclic sulfate 6 and its sulfamide analogue 5, were compared for inhibition of human CA-II. A colorimetric assay, based on the pH shift that accompanies hydration of carbon dioxide, and an esterase assay were used. For these bioisosteric pairs, 1/4 and 6/5, the sulfamate compound was markedly more potent than its sulfamide counterpart. A similar, large difference in potency was also observed for the sulfamate/sulfamide pairs 14/15 and 16/17. These results indicate that the sulfamide moiety is not particularly suitable for obtaining potent carbonic anhydrase inhibition. A discussion of this structure-activity relationship with respect to the interactions of 1 and 6 with CA-II from published X-ray data is presented. A metabolic acidosis study was performed in rats with 1, 4, 6, and 2, and the results are discussed with respect to the degree of inhibition of CA-II in vivo.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
TopiramateCarbonic anhydrase 2ProteinHumans
Yes
Inhibitor
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 2Ki (nM)18N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)3.3N/AN/ADetails
Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose EsterCarbonic anhydrase 2Ki (nM)38N/AN/ADetails
Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose EsterCarbonic anhydrase 2Ki (nM)750N/AN/ADetails
Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose EsterCarbonic anhydrase 2Ki (nM)910N/AN/ADetails
Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose EsterCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)500N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)7700N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)430N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)9600N/AN/ADetails