Bioassay‐Guided Isolation of Antiplasmodial Compounds from Hypericum lanceolatum Lam. (Hypericaceae) and Their Cytotoxicity and Molecular Docking

Abstract

In Cameroon, malaria is still the cause of several deaths yearly and leading to the continued search for new potent leads to fight against Plasmodium falciparum. Medicinal plants like Hypericum lanceolatum Lam. are introduced in local preparations for the treatment of affected people. The bioassay-guided fractionation of the crude extract of the twigs and stem bark of H. lanceolatum Lam. led to the identification of the dichloromethane-soluble fraction as the most active (with 32.6% of the parasite P. falciparum 3D7 survival) which was further purified by successive column chromatography to obtain four compounds identified by their spectrometric data as two xanthones 1,6-dihydroxyxanthone (1) and norathyriol (2) and two triterpenes betulinic acid (3) and ursolic acid (4). In the antiplasmodial assay against P. falciparum 3D7, the triterpenoids 3 and 4 displayed the most significant potencies with IC50 values of 2.8 ± 0.8 μg/mL and 11.8 ± 3.2 μg/mL, respectively. Furthermore, both compounds were also the most cytotoxic against P388 cell lines with IC50 values of 6.8 ± 2.2 μg/mL and 2.5 ± 0.6 μg/mL, respectively. Further insights on the inhibition method of the bioactive compounds and their drug-likeness were obtained from their molecular docking and ADMET studies. The results obtained help in identifying additional antiplasmodial agents from H. lanceolatum and support its use in folk medicine for the treatment of malaria. The plant might be considered as a promising source of new antiplasmodial candidates in new drug discovery.

Cytotoxic and Antioxidant Potential of Launaea mucronata Forssk Essential Oil Growing in Northern Saudi Arabia

“…As a result, eicosane had a limited ability to bind to the target enzymes (Figures 1 and 2). The molecular docking analysis validated the L. mucronata EO's promising antiproliferative action, which may be explained by the compound's farnesyl acetone and farnesol content, as these demonstrated increased binding affinity for the target enzymes [40][41][42].…”

“…SwissADME was used to evaluate the drug-likeness of the compounds based on guidelines considering various descriptors, such as molecular weight, lipophilicity, solubility, flexibility, and topological surface area. Lipophilicity and solubility are essential parameters for drug absorption, while the number of rotatable bonds should be less than 10 for drug-likeness, according to Veber's rule [40][41][42]. Unsaturation in compounds can improve receptor-ligand complementarity.…”

“…Farnesol and farnesyl acetone, on the other hand, showed better ADME profiles by incorporating polar moieties, such as hydroxyl and carbonyl groups, which increased their TPSA values (Table 4). Therefore, adding polar functional groups is crucial for increasing bioavailability [40,41].…”