Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides derived from 4-isothiocyanato-benzolamide.
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Cecchi A, Winum JY, Innocenti A, Vullo D, Montero JL, Scozzafava A, Supuran CT
Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides derived from 4-isothiocyanato-benzolamide.
Bioorg Med Chem Lett. 2004 Dec 6;14(23):5775-80.
- PubMed ID
- 15501039 [ View in PubMed]
- Abstract
A series of sulfonamides incorporating 4-thioureido-benzolamide moieties have been prepared from aminobenzolamide and thiophosgene followed by the reaction of the thiocyanato intermediate with aliphatic/aromatic amines or hydrazines. The new derivatives have been investigated as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), and more precisely of the cytosolic isozymes hCA I and II, as well as the tumor-associated isozyme hCA IX (all of human origin). The new compounds showed excellent inhibitory properties against all three isozymes with inhibition constants in the range of 0.6-62 nM against hCA I, 0.5-1.7 nM against hCA II and 3.2-23 nM against hCA IX, respectively. These derivatives are interesting candidates for the development of novel therapies targeting hypoxic tumors.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 5-[(phenylsulfonyl)amino]-1,3,4-thiadiazole-2-sulfonamide Carbonic anhydrase 2 Ki (nM) 9 N/A N/A Details Acetazolamide Carbonic anhydrase 1 Ki (nM) 900 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 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 Ethoxzolamide Carbonic anhydrase 1 Ki (nM) 25 N/A N/A Details Ethoxzolamide Carbonic anhydrase 2 Ki (nM) 8 N/A N/A Details