Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/membrane-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides incorporating hydrazino moieties.
Article Details
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Winum JY, Dogne JM, Casini A, de Leval X, Montero JL, Scozzafava A, Vullo D, Innocenti A, Supuran CT
Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/membrane-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides incorporating hydrazino moieties.
J Med Chem. 2005 Mar 24;48(6):2121-5.
- PubMed ID
- 15771455 [ View in PubMed]
- Abstract
Targeting proteins overexpressed in hypoxic tumors is as an important means of controlling cancer disease. One such protein is the carbonic anhydrase (CA) isoenzyme IX, which in some types of tumors is overexpressed 150-200-fold. We report here a series of sulfonamide derivatives, prepared from 2-carbohydrazido- and 4-carbohydrazido-benzenesulfonamides, which were further derivatized by reaction with aryl isocyanates or arylsulfonyl isocyanates. Several low nanomolar CA IX inhibitors were detected in this way. SAR is discussed for the diverse types of inhibitors and their affinity for different isozymes, with the aim of obtaining isozyme-specific CA IX inhibitors, with putative applications as antitumor drugs.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 7.5 20 Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 7.5 20 Details Brinzolamide Carbonic anhydrase 2 Ki (nM) 3 7.5 20 Details Diclofenamide Carbonic anhydrase 1 Ki (nM) 1200 7.5 20 Details Diclofenamide Carbonic anhydrase 2 Ki (nM) 38 7.5 20 Details Dorzolamide Carbonic anhydrase 1 Ki (nM) 50000 7.5 20 Details Dorzolamide Carbonic anhydrase 2 Ki (nM) 9 7.5 20 Details Ethoxzolamide Carbonic anhydrase 1 Ki (nM) 25 7.5 20 Details Ethoxzolamide Carbonic anhydrase 2 Ki (nM) 8 7.5 20 Details Methazolamide Carbonic anhydrase 1 Ki (nM) 50 7.5 20 Details Methazolamide Carbonic anhydrase 2 Ki (nM) 14 7.5 20 Details