We describe the characterisation of a series of 4,40-biphenylsulfonamides as selective inhibitors of matrix metalloproteases MMP-2 and -13, two enzymes involved in cell invasion and angiogenesis. Double-inhibitor studies in the presence of acetohydroxamic acid show that these molecules do not bind the catalytic zinc. Moreover, two of the characterised inhibitors (11 and 19) act as non-competitive inhibitors, whereas the para-methyl ester derivative 13 behaves as a competitive inhibitor. This finding suggests that this class of molecules binds to a catalytic subsite, possibly the S10-pocket. Moreover, since these compounds also act as inhibitors of carbonic anhydrases (CAs), another family of enzymes involved in cell invasion, they could be potentially useful as CA/MMP dual target inhibitors with increased efficacy as anticancer agents.

Kinetic characterization of 4,4′-biphenylsulfonamides as selective non-zinc binding MMP inhibitors

NUTI, ELISA;ROSSELLO, ARMANDO
2015

Abstract

We describe the characterisation of a series of 4,40-biphenylsulfonamides as selective inhibitors of matrix metalloproteases MMP-2 and -13, two enzymes involved in cell invasion and angiogenesis. Double-inhibitor studies in the presence of acetohydroxamic acid show that these molecules do not bind the catalytic zinc. Moreover, two of the characterised inhibitors (11 and 19) act as non-competitive inhibitors, whereas the para-methyl ester derivative 13 behaves as a competitive inhibitor. This finding suggests that this class of molecules binds to a catalytic subsite, possibly the S10-pocket. Moreover, since these compounds also act as inhibitors of carbonic anhydrases (CAs), another family of enzymes involved in cell invasion, they could be potentially useful as CA/MMP dual target inhibitors with increased efficacy as anticancer agents.
Salvatore, Santamaria; Nuti, Elisa; Giovanni, Cercignani; Giuseppe La, Regina; Romano, Silvestri; Claudiu T., Supuran; Rossello, Armando
File in questo prodotto:
File Dimensione Formato  
Santamaria 2015.pdf

solo utenti autorizzati

Tipologia: Versione finale editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.06 MB
Formato Adobe PDF
1.06 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: http://hdl.handle.net/11568/739069
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 11
social impact