Carbonic anhydrase inhibitors: design of spin-labeled sulfonamides incorporating TEMPO moieties as probes for cytosolic or transmembrane isozymes.

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.
Authors	Alessandro Cecchi, Laura Ciani, Jean-Yves Winum, Jean-Louis Montero, Andrea Scozzafava, Sandra Ristori, Claudiu T Supuran
Journal	Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 12 Pg. 3475-80 (Jun 15 2008) ISSN: 1464-3405 [Electronic] England
PMID	18513964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, Neoplasm Carbonic Anhydrase Inhibitors Cyclic N-Oxides Free Radicals Isoenzymes Recombinant Proteins Spin Labels Sulfonamides Carbonic Anhydrase II CA9 protein, human Carbonic Anhydrase IX Carbonic Anhydrases TEMPO
Topics	Antigens, Neoplasm (chemistry, drug effects) Carbonic Anhydrase II (antagonists & inhibitors, chemistry) Carbonic Anhydrase IX Carbonic Anhydrase Inhibitors (chemical synthesis, chemistry, pharmacology) Carbonic Anhydrases (chemistry, drug effects) Cell Membrane (drug effects, enzymology) Cyclic N-Oxides (chemistry) Cytosol (drug effects, enzymology) Drug Design Drug Evaluation, Preclinical Free Radicals (chemical synthesis, chemistry, pharmacology) Humans Isoenzymes (antagonists & inhibitors, chemistry) Molecular Structure Recombinant Proteins (drug effects) Spin Labels Stereoisomerism Structure-Activity Relationship Sulfonamides (chemical synthesis, chemistry, pharmacology)

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