title: Natural product hybrid and its superacid synthesized analogues: dodoneine and its derivatives show selective inhibition of carbonic anhydrase isoforms I, III, XIII and XIV.
abstract: The natural product dodoneine (a dihydropyranone phenolic compound), extracted from African mistletoe Agelanthus dodoneifolius, has been investigated as inhibitor of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. By using superacid chemistry, analogues of the lactone phenolic hybrid lead compound have been synthesized and tested as CA inhibitors. Small chemical modifications of the basic scaffold revealed strong changes in the selectivity profile against different CA isoforms. These new compounds selectively inhibited isoforms CA I (K(I)s in the range of 0.13-0.76 μM), III (K(I)s in the range of 5.13-10.80 μM), XIII (K(I)s in the range of 0.34-0.96 μM) and XIV (K(I)s in the range of 2.44-7.24 μM), and can be considered as new leads, probably acting as non-zinc-binders, similar to other phenols/lactones investigated earlier.
authors.affiliation: Superacid Group in Organic Synthesis Team-Université de Poitiers, CNRS UMR 7285 IC2MP, 4, Avenue Michel Brunet, F-86022 Poitiers Cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Carreyre
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Coustard
authors.forename: Grégoire
authors.initials: G
authors.lastname: Carré
authors.forename: Clarisse
authors.initials: C
authors.lastname: Vandebrouck
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Bescond
authors.forename: Maurice
authors.initials: M
authors.lastname: Ouédraogo
authors.forename: Jérôme
authors.initials: J
authors.lastname: Marrot
authors.forename: Daniella
authors.initials: D
authors.lastname: Vullo
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Sébastien
authors.initials: S
authors.lastname: Thibaudeau
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D006801:Humans; D028183:Loranthaceae / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D010636:Phenols; D010936:Plant Extracts; D020033:Protein Isoforms; D002256:Carbonic Anhydrases