Carbonic anhydrase inhibitors: inhibition of isozymes I, II, and IX with triazole-linked O-glycosides of benzene sulfonamides.
Article Details
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Wilkinson BL, Bornaghi LF, Houston TA, Innocenti A, Vullo D, Supuran CT, Poulsen SA
Carbonic anhydrase inhibitors: inhibition of isozymes I, II, and IX with triazole-linked O-glycosides of benzene sulfonamides.
J Med Chem. 2007 Apr 5;50(7):1651-7. Epub 2007 Mar 8.
- PubMed ID
- 17343373 [ View in PubMed]
- Abstract
We report the synthesis of a series of benzene sulfonamides containing triazole-O-glycoside tails for evaluation as carbonic anhydrase (CA) inhibitors. These glycoconjugates were synthesized by the 1,3-dipolar cycloaddition reaction of 4-azidobenzenesulfonamide with O-propynyl glycosides. Compounds were assessed for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA I and II and the tumor-associated isozyme hCA IX (h = human). Against hCA I these compounds were either micromolar or low-nanomolar inhibitors, while against hCA II and IX inhibition in the range of 6.8-53 and 9.7-107 nM, respectively, was observed. The most potent inhibitor against hCA IX was the galactose derivative 8 (Ki = 9.7 nM); this is so far the most potent glycoconjugate inhibitor reported for the tumor-associated hCA IX. These carbohydrate-tethered sulfonamides may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 900 7.5 25 Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 7.5 25 Details Brinzolamide Carbonic anhydrase 1 Ki (nM) 15 7.5 25 Details Brinzolamide Carbonic anhydrase 2 Ki (nM) 9 7.5 25 Details Diclofenamide Carbonic anhydrase 1 Ki (nM) 1200 7.5 25 Details Diclofenamide Carbonic anhydrase 2 Ki (nM) 38 7.5 25 Details Ethoxzolamide Carbonic anhydrase 1 Ki (nM) 25 7.5 25 Details Ethoxzolamide Carbonic anhydrase 2 Ki (nM) 8 7.5 25 Details Methazolamide Carbonic anhydrase 1 Ki (nM) 780 7.5 25 Details Methazolamide Carbonic anhydrase 2 Ki (nM) 14 7.5 25 Details