Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with polyfluorinated aromatic/heterocyclic sulfonamides.

Abstract	The tumor-associated transmembrane carbonic anhydrase (CA, EC 4.2.1.1) isozymes IX (CA IX) and XII (CA XII) are involved in acidification of hypoxic tumors, a process correlated with poor prognosis and clinical outcome of patients harboring such tumors. This process may be reversed by inhibiting these enzymes with potent sulfonamide/sulfamate inhibitors. A series of such aromatic/heterocyclic sulfonamides incorporating 2,3,5,6-tetrafluorobenzoyl-, 2,3,5,6-tetrafluorophenylsulfonyl- and pentafluorophenylureido moieties has been investigated for its interaction with the catalytic domain of the human isozymes hCA IX and hCA XII. Some of these compounds showed excellent inhibitory properties against both isozymes IX and XII, with several subnanomolar inhibitors detected for the first time. These sulfonamides may constitute valuable candidates for the development of novel antitumor therapies based on the inhibition of such tumor-associated CA isozymes.
Authors	Silvia Pastorekova, Daniela Vullo, Angela Casini, Andrea Scozzafava, Jaromir Pastorek, Isao Nishimori, Claudiu T Supuran
Journal	Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 20 Issue 3 Pg. 211-7 (Jun 2005) ISSN: 1475-6366 [Print] England
PMID	16119190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, Neoplasm Carbonic Anhydrase Inhibitors Enzyme Inhibitors Fluorocarbon Polymers Heterocyclic Compounds Isoenzymes Sulfonamides CA9 protein, human Carbonic Anhydrase IX Carbonic Anhydrases carbonic anhydrase XII
Topics	Antigens, Neoplasm (chemistry, metabolism) Carbonic Anhydrase IX Carbonic Anhydrase Inhibitors (chemistry, pharmacology) Carbonic Anhydrases (chemistry, metabolism) Catalytic Domain Cloning, Molecular Enzyme Inhibitors (chemistry, pharmacology) Fluorocarbon Polymers (chemistry) Heterocyclic Compounds Humans Isoenzymes (antagonists & inhibitors, chemistry) Kinetics Structure-Activity Relationship Sulfonamides (chemistry, pharmacology)

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