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

• Published in: Journal of natural products (Washington, D.C.) Vol. 80; no. 6; pp. 1750 - 1757
• Main Authors: Ledoux, Allison, St-Gelais, Alexis, Cieckiewicz, Ewa, Jansen, Olivia, Bordignon, Annélise, Illien, Bertrand, Di Giovanni, Nicolas, Marvilliers, Arnaud, Hoareau, Floriane, Pendeville, Hélène, Quetin-Leclercq, Joëlle, Frédérich, Michel
• Format: Journal Article Web Resource
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 23-06-2017; American Chemical Society
• Subjects: Anacardiaceae - chemistry; Animals; Antimalarials - chemistry; Antimalarials - isolation & purification; Antimalarials - pharmacology; Belgium; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Chemical Sciences; Cyclohexanones - chemistry; Cyclohexanones - isolation & purification; Cyclohexanones - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Flavonoids - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; HeLa Cells; Humans; Inhibitory Concentration 50; Life Sciences; Malaria - drug therapy; Medication; Medicinal Chemistry; Mice; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Parasitic Sensitivity Tests; Pharmaceutical sciences; Plant Leaves - chemistry; Plasmodium berghei - drug effects; Plasmodium falciparum - drug effects; Quercetin - analogs & derivatives; Quercetin - chemistry; Quercetin - pharmacology; Sciences du vivant; Zebrafish - embryology; Poupartia borbonica; Alkyl Cyclohexenone Derivatives
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.6b01019

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.