New 1,1′-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1–21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1′-biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.

Discovery of 1,1'-biiphenyl-4-sulfonamides as a new class of potent and selective carbonic anhydrase XIV inhibitors / LA REGINA, Giuseppe; Coluccia, Antonio; Famiglini, Valeria; Pelliccia, Sveva; Monti, Ludovica; Vullo, Daniela; Nuti, Elisa; Alterio, Vincenzo; De Simone, Giuseppina; Monti, Simona Maria; Pan, Peiwen; Parkkila, Seppo; Supuran, Claudiu T.; Rossello, Armando; Silvestri, Romano. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 58:21(2015), pp. 8564-8572. [10.1021/acs.jmedchem.5b01144]

Discovery of 1,1'-biiphenyl-4-sulfonamides as a new class of potent and selective carbonic anhydrase XIV inhibitors

LA REGINA, GIUSEPPE;COLUCCIA, Antonio;FAMIGLINI, VALERIA;PELLICCIA, SVEVA;MONTI, LUDOVICA;SILVESTRI, Romano
2015

Abstract

New 1,1′-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1–21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1′-biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.
2015
drug design; IX; cristallography; activators; targets
01 Pubblicazione su rivista::01a Articolo in rivista
Discovery of 1,1'-biiphenyl-4-sulfonamides as a new class of potent and selective carbonic anhydrase XIV inhibitors / LA REGINA, Giuseppe; Coluccia, Antonio; Famiglini, Valeria; Pelliccia, Sveva; Monti, Ludovica; Vullo, Daniela; Nuti, Elisa; Alterio, Vincenzo; De Simone, Giuseppina; Monti, Simona Maria; Pan, Peiwen; Parkkila, Seppo; Supuran, Claudiu T.; Rossello, Armando; Silvestri, Romano. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 58:21(2015), pp. 8564-8572. [10.1021/acs.jmedchem.5b01144]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/845349
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