• 통합자연과학논문집
• /
• 제10권1호
• /
• pp.1-6
• /
• 2017

Demand for a new anti-malarial drug has been dramatically increasing in the recent years. Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) plays a vital role in fatty acid elongation process, which now emerged as a new important target for the development of anti-microbial and anti-parasitic molecules. In the present study, 19 compounds namely alginic acid, atropine, chlorogenic acid, chrotacumine A & B, coenzyme $Q_1$, 4-coumaric acid, curcumin, ellagic acid, embelin, 5-O-methyl embelin, eugenyl glucoside, glabridin, hyoscyamine, nordihydroguaiaretic acid, rohitukine, scopolamine, tlatlancuayin and ursolic acid were evaluated on their docking behaviour on P. falciparum enoyl-acyl carrier protein reductase (PfENR) using Auto dock 4.2. The docking studies and binding free energy calculations exhibited that glabridin gave the highest binding energy (-8.07 kcal/mol) and 4-coumaric acid in contrast showed the least binding energy (-4.83 kcal/mol). All ligands except alginic acid, ellagic acid, hyoscyamine and glabridin interacted with Gln409 amino acid residue. Interestingly four ligands namely coenzyme $Q_1$, 4-coumaric acid, embelin and 5-O-methyl embelin interacted with Gln409 amino acid residue present in both chains (A & B) of PfENR protein. Thus, the results of this present study exhibited the potential of these 19 ligands as P. falciparum enoyl-acyl carrier protein reductase (PfENR) inhibitory agents and also as anti-malarial agents.

• Natural Product Sciences
• /
• 제28권2호
• /
• pp.45-52
• /
• 2022

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.