Carbonic anhydrase I and II activation with mono- and dihalogenated histamine derivatives

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• 作者：Mohamed-Chiheb Saada^a ; Daniela Vullo^b ; Jean-Louis Montero^a ; Andrea Scozzafava^b ; Jean-Yves Winum^a ; ^{jean-yves.winum@univ-montp2.fr"" rel=""nofollow} ; Claudiu T. Supuran^b ; ^{claudiu.supuran@unifi.it"" rel=""nofollow}
• 关键词：Carbonic anhydrase ; Enzyme activator ; Histamine ; Halogenated histamine ; Cytosolic isoforms I and II
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 August 2011
• 年：2011
• 卷：21
• 期：16
• 页码：4884-4887
• 全文大小：362 K

文摘

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.