Abstract
The plant Chenopodium opulifolium is traditionally consumed as a food and for treating ailments. Despite its use in Uganda for treating malaria, there are no scientific studies on its phytochemicals and biological potential to ascertain its folkloric claims. In this study, bioassay (antiplasmodial activity) – guided fractionation, isolation and identification of the phytoconstituents of the leaves of C. opulifolium were carried out. The identified compounds were further investigated via in silico docking to propose the mechanism of action of the extracts. The leaves were extracted sequentially via maceration with n-hexane (HEX), dichloromethane (DCM), ethyl acetate (EtOAc), methanol (MeOH), and water. The most active MeOH and DCM extracts were fractionated via chromatography and the compounds were identified via 1D and 2D NMR, FTIR, and GC-MS techniques. The extracts and isolated compounds were tested against the P. falciparum 3D7 strain and clinical field isolates KOM_234 and KDH_204 via a fluorescence-based SYBR Green 1 assay technique. Docking was performed in the active and nucleoside binding sites of the plasmodial lactate dehydrogenase PfLDH. The five extracts showed activity against the P. falciparum 3D7 strain. The MeOH and DCM extracts were the most active with IC(50) values of 0.1177 and 1.189 µg/mL respectively. In P. falciparum clinical field isolates KOM_234 and KDH_204, the MeOH extract had IC(50) values of 5.30 µg/mL and 5.06 µg/mL respectively whereas allantoin from the MeOH extract had an IC(50) value of 2.29 µg/mL and 10.94 µg/mL respectively. Among the identified and isolated compounds 2-myristynoyl pantetheine showed the best binding affinity (-8.3674) for plasmodial dehydrogenase (chloroquine = -6.3451). The antiplasmodial activities of the extract and the identified compounds of C. opulifolium leaves rationalize the traditional use of the plant in malaria therapy. The activity of the extracts can be attributed to the collective constituents principally 2-myristynoyl pantetheine which binds to PfLDH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-026-05361-y.