Natural product hybrid and its superacid synthesized analogues: Dodoneine and its derivatives show selective inhibition of carbonic anhydrase isoforms I,III, XIII and XIV |
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| Authors: | Hélène Carreyre Jean-Marie Coustard Grégoire Carré Clarisse Vandebrouck Jocelyn Bescond Maurice Ouédraogo Jérôme Marrot Daniella Vullo Claudiu T Supuran Sébastien Thibaudeau |
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| Institution: | 1. Superacid Group in Organic Synthesis Team—Université de Poitiers, CNRS UMR 7285 IC2MP, 4, Avenue Michel Brunet, F-86022 Poitiers Cedex, France;2. Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, FRE 3511, 1 rue Georges Bonnet, F-86022 Poitiers Cedex, France;3. Université de Ouagadougou, 03 BP 7021, Ouagadougou 01, Burkina Faso;4. Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles St-Quentin, 45 avenue des Etats Unis, 78035 Versailles Cedex, France;5. Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy;6. Università degli Studi di Firenze, Neurofarba Department, Section of Pharmaceutical Sciences, Via Ugo Schiff 6, I-50019 Sesto Fiorentino (Firenze), Italy |
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| 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 (KIs in the range of 0.13–0.76 μM), III (KIs in the range of 5.13–10.80 μM), XIII (KIs in the range of 0.34–0.96 μM) and XIV (KIs 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. |
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| Keywords: | Dodoneine Superacid Metabolites Carbonic anhydrase Hybrid molecules |
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