Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca2+ Current Inhibitors for Hypotensive Agent Discovery
Hélène Carreyre,
Grégoire Carré,
Maurice Ouedraogo,
Clarisse Vandebrouck,
Jocelyn Bescond,
Claudiu T. Supuran,
Sébastien Thibaudeau
Affiliations
Hélène Carreyre
Superacid Group/Organic Synthesis Team, Université de Poitiers, IC2MP—UMR CNRS 7285, 86073 Poitiers CEDEX 09, France
Grégoire Carré
STIM—ERL CNRS 7368 Université de Poitiers, 86073 Poitiers Cedex 9, France
Maurice Ouedraogo
Laboratoire de Physiologie Animale, Université de Ouagadougou, 03 BP 7021 Ouagadougou 01, Burkina Faso
Clarisse Vandebrouck
STIM—ERL CNRS 7368 Université de Poitiers, 86073 Poitiers Cedex 9, France
Jocelyn Bescond
STIM—ERL CNRS 7368 Université de Poitiers, 86073 Poitiers Cedex 9, France
Claudiu T. Supuran
Department of Neurofarba, Sez, Chimica Farmaceutica e Nutraceutica, University of Florence, 50019 Sesto Fiorentino, Italy
Sébastien Thibaudeau
Superacid Group/Organic Synthesis Team, Université de Poitiers, IC2MP—UMR CNRS 7285, 86073 Poitiers CEDEX 09, France
Dodoneine (Ddn) is one of the active compounds identified from Agelanthus dodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine’s vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III) and L-type Ca2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.
