DOI: https://doi.org/10.55373/mjchem.v26i1.120

Keywords: Diospyros adenophora; Ebenaceae; triterpenoids; anti-malarial activity, β-hematin inhibitor

Abstract

Malaria remains the number one killer disease publicly, leading to the search for a new potent agent that fights against plasmodial falciparum. Diospyros Adenophora (Ebenaceae) is a shrub or tree grown primarily in the wet tropical biome including Peninsula Malaysia. The species of Diospyros have been reported to exhibit interesting biological properties such as antimalaria. Interestingly, no scientific report was documented on the species D. adenophora. In the present study, three known pentacyclic triterpenoids namely lupenone (1), lupeol (2), and betulin (3) were isolated from this species and fully characterized using extensive spectroscopic data like 1D- and 2D- nuclear magnetic resonance (NMR) as well as FT-IR and HRESIMS and subsequently compared with the reported literature. All compounds were screened in vitro for anti-malarial activity against β-hematin polymerization inhibition as well as molecular docking. The in vitro analysis revealed that compound 2 is the most active, with an IC50 value of 20.2 ± 17 μM, followed by compound 1 having an IC50 value of 27.5 ± 23 μM. These compounds have a lower IC50 value than chloroquine (37.5 ± 0.6 μM) as a control. Compound 3 exhibits moderate activity (IC50: 40.9 ± 22 μM) in comparison to the control. In addition, all compounds displayed high binding energy in comparison to standard chloroquine (-7.7 kcal/mol), as determined by molecular docking data. The total binding energy of lupenone (1) and betulin (3) with hemozoin crystal is -8.6 and -9.2 kcal/mol, respectively. While lupeol (2) was observed to have a high binding energy at -9.7 kcal/mol, it is considered the best binding interaction with hemozoin crystal. Based on the results obtained from in vitro β-hematin polymerization inhibition and the in-silico analysis, compounds 1 and 2 are predicted to be potential anti-malarial agents.