Two Coumarin Compounds Isolated from Scadoxus Multiflorus as a Potential Therapeutic Candidates against Plasmodium Falciparum Enzymes through Insilco Approach

The rising incidence of Plasmodium falciparum resistance to existing antimalarial drugs continues to undermine global malaria control efforts, particularly in developing countries where the disease remains a major cause of morbidity and mortality. Given the emergence of drug-resistant strains and the limited pipeline of new therapeutic leads, the search for novel antimalarial agents from natural sources is of critical importance. In this study, two coumarin derivatives isolated from Scadoxus multiflorus were investigated for their potential antimalarial activity using an in-silico approach. The molecular structures of the compounds were generated with ChemDraw and energy-minimized using Spartan14. Their pharmacokinetic properties and toxicity profiles were predicted using SwissADME and ProTox 3.0, respectively. Molecular docking was conducted with AutoDock Vina to evaluate binding interactions with key P. falciparum enzymes, including Falcipain-2, Falcipain-3, and Plasmepsin-2. Compound B12 (2-methyl-2H-chromen-7-ol) exhibited binding affinities between − 5.3 and − 5.6 kcal/mol, whereas compound C11 (7- methoxy-2H-chromen-2-one) demonstrated slightly stronger affinities ranging from − 5.9 to − 5.6 kcal/mol. Both compounds engaged in favorable hydrogen bonding, van der Waals interactions, and π–π stacking with active-site residues. Drug-likeness assessments confirmed compliance with Lipinski’s rule of five, and toxicity predictions revealed acceptable safety margins (LD50: 500 mg/kg for B12 and 4300 mg/kg for C11). Collectively, these findings suggest that the tested coumarin derivatives possess desirable pharmacological properties and a multi-target binding profile, supporting their candidacy for further development as antimalarial agents. Experimental validation through in vitro and in vivo studies is warranted to confirm their therapeutic potential and advance them toward clinical applicability.