Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozymes IX and XII with a library of aromatic and heteroaromatic sulfonamides.
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Ozensoy O, Puccetti L, Fasolis G, Arslan O, Scozzafava A, Supuran CT
Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozymes IX and XII with a library of aromatic and heteroaromatic sulfonamides.
Bioorg Med Chem Lett. 2005 Nov 1;15(21):4862-6.
- PubMed ID
- 16168653 [ View in PubMed]
- Abstract
The inhibition of the two transmembrane, tumor-associated isozymes of carbonic anhydrase (CA, EC 4.2.1.1) of human origin, hCA IX and XII, with a library of aromatic and heteroaromatic sulfonamides has been investigated. Most of them were sulfanilamide, homosulfanilamide, and 4-aminoethyl-benzenesulfonamide derivatives, to which tails that should induce diverse physico-chemical properties have been attached at the amino moiety, whereas several of these compounds were derived from metanilamide, benzene-1,3-disulfonamide or the 1,3,4-thiadiazole/thiadiazoline-2-sulfonamides. The tails were of the alkyl/aryl-carboxamido/sulfonamido-, ureido or thioureido type. Against hCA IX the investigated compounds showed inhibition constants in the range of 3-294 nM, whereas against hCA XII in the range of 1.9-348 nM, respectively. The best hCA IX inhibitors were ureas/thioureas incorporating 4-aminoethyl-benzenesulfonamide and metanilamide moieties. The best hCA XII inhibitors were 1,3,4-thiadiazole/thiadiazoline-2-sulfonamides incorporating 5-acylamido or 5-arylsulfonylamido moieties. These compounds also inhibited appreciably the cytosolic isozymes hCA I and II, but some selectivity for the transmembrane, tumor-associated isozymes was observed for some of them, which is an encouraging result for the design of novel therapies targeting hypoxic tumors, in which these carbonic anhydrases are highly overexpressed.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Acetazolamide Carbonic anhydrase 12 Ki (nM) 5.7 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 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