Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform.
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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
Drug Target Kind Organism Pharmacological Action Actions Topiramate Carbonic anhydrase 2 Protein Humans YesInhibitorDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 2 Ki (nM) 18 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 3.3 N/A N/A Details Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose Ester Carbonic anhydrase 2 Ki (nM) 38 N/A N/A Details Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose Ester Carbonic anhydrase 2 Ki (nM) 750 N/A N/A Details Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose Ester Carbonic anhydrase 2 Ki (nM) 910 N/A N/A Details Sulfamic Acid 2,3-O-(1-Methylethylidene)-4,5-O-Sulfonyl-Beta-Fructopyranose Ester Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 500 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 7700 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 430 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 9600 N/A N/A Details