Publication

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

Winum, JY., Dogne, JM., Casini, A., de Leval, X., Montero, JL., Scozzafava, A., Vullo, D., Innocenti, A. & Supuran, CT., 24-Mar-2005, In : Journal of Medicinal Chemistry. 48, 6, p. 2121-2125 5 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • JY Winum
  • JM Dogne
  • A Casini
  • X. de Leval
  • JL Montero
  • A Scozzafava
  • D Vullo
  • A Innocenti
  • CT Supuran

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.

Original languageEnglish
Pages (from-to)2121-2125
Number of pages5
JournalJournal of Medicinal Chemistry
Volume48
Issue number6
Publication statusPublished - 24-Mar-2005
Externally publishedYes

    Keywords

  • RAY CRYSTALLOGRAPHIC STRUCTURE, PRESSURE-LOWERING AGENTS, AROMATIC/HETEROCYCLIC SULFONAMIDES, HETEROCYCLIC SULFONAMIDES, SELECTIVE INHIBITORS, TRANSMEMBRANE, ANTICANCER, ADDUCT, DERIVATIVES, THERAPY

ID: 14997552