Antimalarial Activities of Alkyl Cyclohexenone Derivatives Isolated from the Leaves of Poupartia borbonica

J Nat Prod. 2017 Jun 23;80(6):1750-1757. doi: 10.1021/acs.jnatprod.6b01019.

Allison Ledoux ¹, Alexis St-Gelais ¹ ², Ewa Cieckiewicz ¹, Olivia Jansen ¹, Annélise Bordignon ¹, Bertrand Illien ³, Nicolas Di Giovanni ⁴, Arnaud Marvilliers ³, Floriane Hoareau ³, Hélène Pendeville ⁵, Joëlle Quetin-Leclercq ⁶, Michel Frédérich ¹

Affiliations

1 Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège , Avenue Hippocrate 15, 4000 Liège, Belgium.
2 Laboratoire d'Analyses et de Séparation des Essences Végétales (LASEVE), Université du Québec à Chicoutimi , 555 Boulevard de l'Université, Saguenay, Québec G7H 2B1, Canada.
3 Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments (LCSNA), University of Reunion Island , Avenue René Cassin 15, 97744 Saint-Denis, La Réunion France.
4 Laboratoire de Chimie Analytique Organique et Biologique (OBiAChem), University of Liège , Allée de la Chimie 3, Sart-Tilman, 4000 Liège, Belgium.
5 Plateforme Zebrafish Facility and Transgenics, GIGA, University of Liège , Avenue Hippocrate 15, 4000 Liège, Belgium.
6 Pharmacognosy Research Group, Louvain Drug Research Institute, Université Catholique de Louvain , Avenue E. Mounier, B1 72.03, B-1200 Brussels, Belgium.

PMID: 28557449 DOI: 10.1021/acs.jnatprod.6b01019

Abstract

Bioactivity-guided fractionation of the ethyl acetate extract of the leaves of Poupartia borbonica led to the isolation of three new alkyl cyclohexenone derivatives 1-3, and named Poupartone A-C. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopic data analysis and MS, whereas calculated and experimental ECD spectra were used to define the absolute configurations. These compounds were active against 3D7 and W2 Plasmodium falciparum strains with IC₅₀ values between 0.55 and 1.81 μM. In vitro cytotoxicity against WI38 human fibroblasts and the human cervical Cancer cell line HeLa (WST-1 assay) showed that these compounds were also cytotoxic, but no hemolytic activity was observed for the extract and pure compounds. An in vivo antimalarial assay was performed on the major cyclohexenone using P. berghei-infected mice at a dose of 15 mg/kg/day IP. The assay revealed growth inhibition of 59.1 and 69.5% at days 5 and 7 postinfection, respectively, although some toxicity was observed. Zebrafish larvae were used as a model to determine the type of toxicity, and the results showed cardiac toxicity. The methanol extract was also studied, and it displayed moderate antiplasmodial properties in vitro. This extract contained the known Flavonoids, quercetin, 3'-O-hydroxysulfonylquercetin, quercitrin, and isoquercitrin as well as ellagic acid, which showed high to low activity against the 3D7 P. falciparum strain.

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