Antiplasmodial and cytotoxic metabolites from the aerial parts of Vernonia glabra (Asteraceae).

The identification of antiplasmodial lead compounds from the aerial parts of Vernonia glabra (Asteraceae) was carried out using a bioassay-directed protocol. The methanolic extract of the plant was partitioned into four main fractions using n-hexane, dichloromethane, ethyl acetate, and n-butanol. These fractions were then tested for their antiplasmodial activity against Plasmodium falciparum 3D7. The bioassay results indicated that the dichloromethane-soluble fraction had the highest potency, with an IC50 of 8.4 ± 0.5 μg/mL. Further purification of the active fraction through successive column chromatography led to the isolation and identification of eleven compounds: three previously undescribed compounds (vernonins X-Z, 1-3) and eight known ones (4-11). The structural characterization of all isolated compounds was conducted using comprehensive 1D and 2D-NMR spectroscopy, as well as high-resolution mass spectrometry (HRMS). The antiplasmodial activity, cytotoxicity, and hemolytic effects of compounds 1-3 and 7-10 were evaluated. Compounds 1, 2, 8, and 9 demonstrated promising antiplasmodial potencies against P. falciparum 3D7, with IC50 values less than 10 μg/mL. However, among these, only compound 8 displayed cytotoxicity against Vero cell lines, with a CC50 of 306.8 ± 1.7 μg/mL (selectivity index [SI] = 39.3). Compounds 1, 2, and 9 did not show any significant cytotoxicity at concentrations up to 1000 μg/mL. Additionally, none of the tested compounds exhibited hemolytic effects on human red blood cells at concentrations up to 100 μg/mL, indicating their safety. These results support the use of V. glabra for malaria treatment and demonstrate that its bioactive metabolites are promising leads in the development of safe and effective antimalarial drugs.