Carbonic anhydrase inhibitors: design of spin-labeled sulfonamides incorporating TEMPO moieties as probes for cytosolic or transmembrane isozymes.
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Cecchi A, Ciani L, Winum JY, Montero JL, Scozzafava A, Ristori S, Supuran CT
Carbonic anhydrase inhibitors: design of spin-labeled sulfonamides incorporating TEMPO moieties as probes for cytosolic or transmembrane isozymes.
Bioorg Med Chem Lett. 2008 Jun 15;18(12):3475-80. doi: 10.1016/j.bmcl.2008.05.051. Epub 2008 May 17.
- PubMed ID
- 18513964 [ View in PubMed]
- Abstract
A series of spin-labeled sulfonamides incorporating TEMPO moieties were synthesized by a procedure involving the formation of a thiourea functionality between the benzenesulfonamide and free radical fragment of the molecules. The new compounds were tested as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and showed efficient inhibition of the physiologically relevant isozymes hCA II and hCA IX (hCA IX being predominantly found in tumors) and moderate to weak inhibitory activity against hCA I. Some derivatives were also selective for inhibiting the tumor-associated isoform over the cytosolic one CA II, and presented significant changes in their ESR signals when complexed to the enzyme active site, being interesting candidates for the investigation of hypoxic tumors overexpressing CA IX by ESR techniques, as well as for imaging/treatment purposes.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 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