A novel series of benzenesulfonamides that contain ferrocenyl or ruthenocenyl moieties were synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant carbonic anhydrase (CA) isozymes: hCA I, II and tumour-associated IX (h=human). This manuscript describes the regioselective synthesis of both the 1,4- and 1,5-disubstituted-1,2,3-triazole benzenesulfonamides from ethynylmetallocene substrates. This is the first report describing the covalent attachment of organometallic moieties to the arylsulfonamide (ArSO(2)NH(2)) CA recognition pharmacophore. At hCA I these metallocene derivatives were either nanomolar or low micromolar inhibitors, while against hCA II and IX inhibition in the range of 9.7-80nM and 10.3-85nM, respectively, was observed. The ruthenocenyl derivatives gave superior CA inhibition compared to the ferrocenyl compounds across all three CA isozymes. These compounds constitute a new organometallic class of CA inhibitors with promising biological activity.

Inhibition of carbonic anhydrase isozymes I, II and IX with benzenesulfonamides containing an organometallic moiety / A. J. Salmon;M. L. Williams;A. Innocenti;D. Vullo;C. T. Supuran;S. Poulsen. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 17:(2007), pp. 5032-5035. [10.1016/j.bmcl.2007.07.024]

Inhibition of carbonic anhydrase isozymes I, II and IX with benzenesulfonamides containing an organometallic moiety.

VULLO, DANIELA;SUPURAN, CLAUDIU TRANDAFIR;
2007

Abstract

A novel series of benzenesulfonamides that contain ferrocenyl or ruthenocenyl moieties were synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant carbonic anhydrase (CA) isozymes: hCA I, II and tumour-associated IX (h=human). This manuscript describes the regioselective synthesis of both the 1,4- and 1,5-disubstituted-1,2,3-triazole benzenesulfonamides from ethynylmetallocene substrates. This is the first report describing the covalent attachment of organometallic moieties to the arylsulfonamide (ArSO(2)NH(2)) CA recognition pharmacophore. At hCA I these metallocene derivatives were either nanomolar or low micromolar inhibitors, while against hCA II and IX inhibition in the range of 9.7-80nM and 10.3-85nM, respectively, was observed. The ruthenocenyl derivatives gave superior CA inhibition compared to the ferrocenyl compounds across all three CA isozymes. These compounds constitute a new organometallic class of CA inhibitors with promising biological activity.
2007
17
5032
5035
A. J. Salmon;M. L. Williams;A. Innocenti;D. Vullo;C. T. Supuran;S. Poulsen
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/776036
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