In-vitro Antimalarial Investigations and Molecular Docking Studies of Compounds from Trema orientalis L. (blume) Leaf Extract

The identification of Plasmodium falciparum enoyl acyl-carrier protein reductase (pfENR) is considered as a potential biological target against malaria. Trema orientalis is considered a rich source of phytochemicals useful in malaria treatment. This study evaluated the in-vitro inhibitory activity of the extract and isolated compounds of T. orientalis leaf; the isolated compounds and the analogues of the most active compound were subjected to in-silico molecular docking studies on pfENR. The methanolic extract of T. orientalis was subjected to repeated chromatographic separation which led to the isolation of some compounds. The isolated compounds from the plant were examined for their antimalarial activity using β-hematin inhibition assay. Virtual screening via molecular docking and ADMET studies were conducted to gain insight into the mechanism of binding of ligand and to identify effective pfENR inhibitors. The isolated compounds and the analogues of the most active isolates were gotten from PubChem library for use in docking study. Hexacosanol and β-sitosterol showed inhibition of the β-hematin formation. The docking results showed that hexacosanol, β-sitosterol and the analogues of β-sitosterol displayed binding energy ranging between -6.1 kcal/mol and -11.6 kcal/mol. Sitosterol glucoside has the highest docking score. Some of the ligands showed more binding affinity than known bioactive compounds used as reference. Analogues of β-sitosterol has been shown to be potential inhibitors of pfENR, therefore, the findings from this study suggest that sitosterol glucoside and ergosterol peroxide could act as antimalarial agents after further lead optimisation investigations.