Muhammad Farid
Departement of Medicine, Faculty of Medicine, Ahmad Dahlan University, Yogyakarta, Indonesia

DOI: https://doi.org/10.19184/ams.v11i3.53732

Abstract

Falciparum malaria, caused by Plasmodium falciparum, remains a major global health threat, complicated by the emergence of drug-resistant strains that undermine the efficacy of current artemisinin-based therapies. Eurycoma longifolia Jack (Pasak Bumi), a medicinal plant native to Southeast Asia, has long been used in traditional medicine for treating malaria and infectious diseases. Given the growing resistance of Plasmodium falciparum to existing antimalarial drugs, exploring novel therapeutic agents has become increasingly important. Since bioactive constituents of Eurycoma longifolia have been reported to interact with cell membranes, this study aims to predict their potential antimalarial activity using a computational approach targeting P. falciparum dihydroorotate dehydrogenase (PfDHODH), a crucial enzyme in the parasite’s pyrimidine biosynthesis pathway. Ten phytochemicals were selected and their 3D structures were prepared using PyRx and Open Babel. Molecular docking simulations were conducted using AutoDock Vina, with artemisinin as a control. Docking validation achieved an RMSD of 0.823 Å, confirming protocol reliability. Among the tested ligands, syringic acid showed the highest binding affinity -6.7 kcal/mol, followed by scopoletin -6.6, and fraxidin -6.4, with key interactions involving residues His185, Val532, and Phe188. Toxicological predictions indicated variability, with 1,1′-biphenyl-3,3′-dicarboxylic acid exhibiting the highest acute toxicity. Despite no compound surpassing the native ligand's binding energy -7.9 kcal/mol, several exhibited promising interactions and favorable safety profiles. This study highlights E. longifolia as a promising source of phytochemicals for antimalarial drug discovery. Further experimental studies and molecular dynamics simulations are recommended to validate these findings and optimize compound efficacy.

Keyword: Eurycoma longifolia, antimalarial, molecular docking, plasmodium falciparum

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