Activation of the human carbonic anhydrase (CA, EC 4.2.1.1) isozymes I, II (cytosolic) and IX (transmembrane, tumor-associated isoform) with a series of arylsulfonylhydrazido-l-histidines incorporating 4-substituted-phenyl, pentafluorophenyl- and beta-naphthyl moieties was investigated. The compounds showed a weak hCA I activation profile, but were more efficient as hCA II and IX activators. The 4-iodophenyl-substituted derivative behaved as a strong and isozyme selective hCA II activator, with an activation constant of 0.21muM. This is the first isoform-selective, potent CA activator reported to date.
Carbonic anhydrase activators: activation of human isozymes I, II and IX with phenylsulfonylhydrazido l-histidine derivatives / M. Abdo;D. Vullo;M. Saada;J. Montero;A. Scozzafava;J. Winum;C. T. Supuran. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 19:(2009), pp. 2440-2443. [10.1016/j.bmcl.2009.03.050]
Carbonic anhydrase activators: activation of human isozymes I, II and IX with phenylsulfonylhydrazido l-histidine derivatives.
VULLO, DANIELA;SCOZZAFAVA, ANDREA;SUPURAN, CLAUDIU TRANDAFIR
2009
Abstract
Activation of the human carbonic anhydrase (CA, EC 4.2.1.1) isozymes I, II (cytosolic) and IX (transmembrane, tumor-associated isoform) with a series of arylsulfonylhydrazido-l-histidines incorporating 4-substituted-phenyl, pentafluorophenyl- and beta-naphthyl moieties was investigated. The compounds showed a weak hCA I activation profile, but were more efficient as hCA II and IX activators. The 4-iodophenyl-substituted derivative behaved as a strong and isozyme selective hCA II activator, with an activation constant of 0.21muM. This is the first isoform-selective, potent CA activator reported to date.
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