Carbonic anhydrase inhibitors (CAIs) of the sulfonamide, sulfamate and coumarin classes bearing the phenylureido tail found in the clinically used drug Sorafenib, a multikinase inhibitor actually used for the management of hepatocellular carcinomas, are reported. All compounds were assayed on human (h) CA isoforms I, II, VII and IX, involved in various pathologies. Among the sulfonamides, several compounds were selective for inhibiting hCA IX, with KI values in the low nanomolar ranges (i.e. 0.7-30.2 nM). We explored the binding modes of such compounds by means of X-ray crystallographic studies on isoform hCA I in adduct with one sulfonamide and a sulfamate inhibitor. Antiproliferative properties of some sulfamates on breast tumor cell lines were also investigated.

Carbonic anhydrase inhibitors based on sorafenib scaffold: Design, synthesis, crystallographic investigation and effects on primary breast cancer cells / Bozdag, Murat; Ferraroni, Marta; Ward, Carol; Carta, Fabrizio; Bua, Silvia; Angeli, Andrea; Langdon, Simon P; Kunkler, Ian H; Al-Tamimi, Abdul-Malek S; Supuran, Claudiu T. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1768-3254. - ELETTRONICO. - 182:(2019), pp. 111600-111611. [10.1016/j.ejmech.2019.111600]

Carbonic anhydrase inhibitors based on sorafenib scaffold: Design, synthesis, crystallographic investigation and effects on primary breast cancer cells

BOZDAG, MURAT;Ferraroni, Marta;Carta, Fabrizio;BUA, SILVIA;ANGELI, ANDREA;Supuran, Claudiu T
2019

Abstract

Carbonic anhydrase inhibitors (CAIs) of the sulfonamide, sulfamate and coumarin classes bearing the phenylureido tail found in the clinically used drug Sorafenib, a multikinase inhibitor actually used for the management of hepatocellular carcinomas, are reported. All compounds were assayed on human (h) CA isoforms I, II, VII and IX, involved in various pathologies. Among the sulfonamides, several compounds were selective for inhibiting hCA IX, with KI values in the low nanomolar ranges (i.e. 0.7-30.2 nM). We explored the binding modes of such compounds by means of X-ray crystallographic studies on isoform hCA I in adduct with one sulfonamide and a sulfamate inhibitor. Antiproliferative properties of some sulfamates on breast tumor cell lines were also investigated.
2019
182
111600
111611
Bozdag, Murat; Ferraroni, Marta; Ward, Carol; Carta, Fabrizio; Bua, Silvia; Angeli, Andrea; Langdon, Simon P; Kunkler, Ian H; Al-Tamimi, Abdul-Malek S; Supuran, Claudiu T
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1170234
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