Carbonic anhydrase inhibitors: Synthesis and inhibition of cytosolic/membrane-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides incorporating hydrazino moieties

J.-Y. Winum, J.-M. Dogné, A. Casini, X. De Leval, J.-L. Montero, A. Scozzafava, D. Vullo, A. Innocenti, C.T. Supuran

Research output: Contribution to journalArticlepeer-review

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. © 2005 American Chemical Society.
Original languageEnglish
Pages (from-to)2121-5
Number of pages5
JournalJournal of Medicinal Chemistry
Volume48
Issue number6
DOIs
Publication statusPublished - 24 Mar 2005

Keywords

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrases
  • Cell Membrane
  • Cytosol
  • Hydrazines
  • Isocyanates
  • Isoenzymes
  • Structure-Activity Relationship
  • Sulfonamides

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