title: Carbonic anhydrase I and II activation with mono- and dihalogenated histamine derivatives.
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.
authors: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
authors: Mohamed-Chiheb
authors: MC
authors: Saada
authors: Daniela
authors: D
authors: Vullo
authors: Jean-Louis
authors: JL
authors: Montero
authors: Andrea
authors: A
authors: Scozzafava
authors: Jean-Yves
authors: JY
authors: Winum
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000378:metabolism*; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006219:Halogens / Q000737:chemistry*; D006632:Histamine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D006219:Halogens; D006632:Histamine; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II