Mono- and dihalogenated histamine derivatives incorporating fluorine, chlorine and bromine have been prepared together with the corresponding boc-protected compounds at the aminoethyl group. They have been investigated as activators of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The cytosolic human (h) isoforms hCA I and II were moderately activated by the boc-protected halogenated histamines and very effectively activated by the deprotected ones. Low nanomolar and subnanomolar hCA I and II activators have been detected for the first time, starting from histamine as lead which has an affinity of 2 μM against isoform I and of 125 μM against hCA II.
Carbonic anhydrase I and II activation with mono- and dihalogenated histamine derivatives / M. Saada;D. Vullo;J. Montero;A. Scozzafava;J. Winum;C. T. Supuran. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 21:(2011), pp. 4884-4887. [10.1016/j.bmcl.2011.06.030]
Carbonic anhydrase I and II activation with mono- and dihalogenated histamine derivatives.
VULLO, DANIELA;SCOZZAFAVA, ANDREA;SUPURAN, CLAUDIU TRANDAFIR
2011
Abstract
Mono- and dihalogenated histamine derivatives incorporating fluorine, chlorine and bromine have been prepared together with the corresponding boc-protected compounds at the aminoethyl group. They have been investigated as activators of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The cytosolic human (h) isoforms hCA I and II were moderately activated by the boc-protected halogenated histamines and very effectively activated by the deprotected ones. Low nanomolar and subnanomolar hCA I and II activators have been detected for the first time, starting from histamine as lead which has an affinity of 2 μM against isoform I and of 125 μM against hCA II.
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