By using SLC-0111 (4-fluorophenylureido-benzenesulfonamide), a sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor in Phase I clinical trials as an antitumor agent as lead molecule, a series of benzenesulfonamide derivatives incorporating ureido moieties was synthesized. The new compounds contain a 4-N-substituted piperazine fragment in which the ureido linker has been included, and were tested as inhibitors of the cytosolic human (h) hCA I and II isoforms, as well as the transmembrane, tumor-associated enzymes hCA IX and XII. Depending on the substitution pattern at the piperazine ring, low nanomolar inhibitors were detected against all four isoforms, making the new class of sulfonamides of interest for various pharmacologic applications.

Synthesis of sulfonamides incorporating piperazinyl-ureido moieties and their carbonic anhydrase I, II, IX and XII inhibitory activity

CONGIU, CENZO;ONNIS, VALENTINA;DEPLANO, ALESSANDRO;BALBONI, GIANFRANCO;
2015

Abstract

By using SLC-0111 (4-fluorophenylureido-benzenesulfonamide), a sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor in Phase I clinical trials as an antitumor agent as lead molecule, a series of benzenesulfonamide derivatives incorporating ureido moieties was synthesized. The new compounds contain a 4-N-substituted piperazine fragment in which the ureido linker has been included, and were tested as inhibitors of the cytosolic human (h) hCA I and II isoforms, as well as the transmembrane, tumor-associated enzymes hCA IX and XII. Depending on the substitution pattern at the piperazine ring, low nanomolar inhibitors were detected against all four isoforms, making the new class of sulfonamides of interest for various pharmacologic applications.
Carbonic anhydrase; Sulfonamide; Inhibitor; Piperazine; Tumor-associated isoform
File in questo prodotto:
File Dimensione Formato  
BMCL_2015_CAI_supporting info.docx

Solo gestori archivio

Descrizione: supplementary informations
Tipologia: altro documento allegato
Dimensione 28.03 kB
Formato Microsoft Word XML
28.03 kB Microsoft Word XML   Visualizza/Apri   Richiedi una copia
BMCL_2015_CAI_supporting info2.xlsx

Solo gestori archivio

Descrizione: supporting information 2
Tipologia: altro documento allegato
Dimensione 299.91 kB
Formato Microsoft Excel XML
299.91 kB Microsoft Excel XML   Visualizza/Apri   Richiedi una copia
BMCL 2015_CAI.pdf

Solo gestori archivio

Descrizione: Articolo principale Versione dell'editore
Tipologia: versione editoriale
Dimensione 1.75 MB
Formato Adobe PDF
1.75 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/113166
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 24
social impact