Carbonic anhydrase activators: Activation of human isozymes I, II and IX with phenylsulfonylhydrazido l-histidine derivatives

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 β-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 0.21 μM. This is the first isoform-selective, potent CA activator reported to date.

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