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

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.