We describe the characterisation of a series of 4,4′-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 S1′-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 / Santamaria, S; Nuti, E; Cercignani, G; LA REGINA, Giuseppe; Silvestri, Romano; Supuran C., T; Rossello, A.. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - STAMPA. - 30:6(2015), pp. 947-954. [10.3109/14756366.2014.1000889]

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

LA REGINA, GIUSEPPE;SILVESTRI, Romano;
2015

Abstract

We describe the characterisation of a series of 4,4′-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 S1′-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.
2015
carbonic anhydrase; matrix metalloproteases: non-competitive inhibitors; non-zinc binding inhibitors
01 Pubblicazione su rivista::01a Articolo in rivista
Kinetic characterization of 4,4'-biphenylsulfonamides as selective non-zinc binding MMP inhibitors / Santamaria, S; Nuti, E; Cercignani, G; LA REGINA, Giuseppe; Silvestri, Romano; Supuran C., T; Rossello, A.. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - STAMPA. - 30:6(2015), pp. 947-954. [10.3109/14756366.2014.1000889]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/780891
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