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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / chemistry*
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Carbonic Anhydrase I / chemistry*
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Carbonic Anhydrase II / chemistry*
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Carbonic Anhydrase IX
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Carbonic Anhydrase Inhibitors / chemical synthesis*
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Carbonic Anhydrase Inhibitors / chemistry
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Carbonic Anhydrases / chemistry*
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Cell Membrane / chemistry
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Cytosol / chemistry
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Hydrazines / chemistry
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Isocyanates / chemical synthesis
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Isocyanates / chemistry
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / chemistry
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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Carbonic Anhydrase Inhibitors
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Hydrazines
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Isocyanates
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Isoenzymes
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Sulfonamides
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Carbonic Anhydrase I
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Carbonic Anhydrase II
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CA9 protein, human
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Carbonic Anhydrase IX
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Carbonic Anhydrases