Carbonic anhydrase inhibitors: hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX (Articolo in rivista)

Type
Label
  • Carbonic anhydrase inhibitors: hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX (Articolo in rivista) (literal)
Anno
  • 2006-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/jm060531j (literal)
Alternative label
  • De Simone Giuseppina; Vitale Rosa Maria; Di Fiore Anna; Pedone Carlo; Scozzafava Andrea; Montero Jean-Louis; Winum Jean-Yves; Supuran Claudiu T (2006)
    Carbonic anhydrase inhibitors: hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX
    in Journal of medicinal chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • De Simone Giuseppina; Vitale Rosa Maria; Di Fiore Anna; Pedone Carlo; Scozzafava Andrea; Montero Jean-Louis; Winum Jean-Yves; Supuran Claudiu T (literal)
Pagina inizio
  • 5544 (literal)
Pagina fine
  • 5551 (literal)
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  • 49 (literal)
Rivista
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  • 18 (literal)
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  • Pubblicazione su rivista scientifica internazionale (literal)
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto di Biostrutture e Bioimmagini CNR, Via Mezzocannone 16, 80134 Naples, Italy; Dipartimento delle Scienze Biologiche-Sezione Biostrutture, University of Naples \"Federico II\", Via Mezzocannone 16, 80134 Naples, Italy; Laboratorio di Chimica Bioinorganica, Rm. 188, UniVersita` degli Studi di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Laboratoire de Chimie Biomolèculaire, UMR 5032, Ecole Nationale Supérieure de Chimie de Montpellier, Université Montpellier II, 8 Rue de l'Ecole Normale, 34296 Montpellier Cedex, France (literal)
Titolo
  • Carbonic anhydrase inhibitors: hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX (literal)
Abstract
  • An approach for designing bioreductive, hypoxia-activatable carbonic anhydrase (CA, EC 4.2.1.1) inhibitors targeting the tumor-associated isoforms is reported. Sulfonamides incorporating 3,3'-dithiodipropionamide/2,2'-dithiodibenzamido moieties were prepared and reduced enzymatically/chemically in conditions present in hypoxic tumors, leading to thiols. The X-ray crystal structure of the most promising compound, 4-(2-mercaptophenylcarboxamido)benzenesulfonamide, which as disulfide showed a KI against hCA IX of 653 nM (in reduced form of 9.1 nM), in adduct with hCA II showed the inhibitor making favorable interactions with Gln92, Val121, Phe131, Leu198, Thr199, Thr200, Pro201, and Pro202, whereas the sulfamoyl moiety was coordinated to the Zn2+ ion. The same interactions were preserved in the adduct with hCA IX, but in addition, a hydrogen bond between the SH moiety of the inhibitor and the amide nitrogen of Gln67 was evidenced, which may explain the almost 2 times more effective inhibition of the tumor-associated isozyme over the cytosolic isoform. (literal)
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