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

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 IC 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.

Flavonoid composition, cellular antioxidant activity and (myelo)peroxidase inhibition of a Bryonia alba L. (Cucurbitaceae) leaves extract

“…Values of the IC 50 were calculated by linear regression, by comparison with the negative control (nontreated cells). Camptothecin was used as a positive reference . Cell viability on the HL‐60 cells was assessed using the [3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) test.…”

“…Embryos were observed until reaching 72 h of development. Negative control consisted in 25 embryos not treated with samples …”

“…Camptothecin was used as a positive reference. [18] Cell viability on the HL-60 cells was assessed using the [3-…”

Heparin-Coated Liposomes Improve Antiplasmodial Activity and Reduce the Toxicity of Poupartone B

“…Consequently, this strategy was applied to poupartone B, which revealed high antiplasmodial activity, but also toxicity, in previous studies [15]. This compound was selected because of the high bioactive potential of this class of compounds, which can be demonstrated further through nanocarrier technology.…”

“…This compound was selected because of the high bioactive potential of this class of compounds, which can be demonstrated further through nanocarrier technology. Indeed, the alkyl cyclohexanone derivatives isolated from some Anacardiaceae, such as Lannea rivae, Lannea welwitshii, Lannea edulis, Taparira guianensis, Taparira obtuse, and, more recently, from the mushroom Hygrophorus abieticola, demonstrated antimalarial, antibacterial, fungicidal, and anticancer activities [15][16][17][18][19]. The aim of this study was to demonstrate the applicability of this formulation in the delivery of an isolated natural compound while minimizing its toxicity and improving its selectivity index, even on a partially artemisinin-resistant strain.…”