Studi In Silico dan Prediksi Aktivitas Senyawa Turunan Chalcone terhadap Protein (PfDHODH) Plasmodium falciparum Dihydroorotate Dehydrogenase sebagai Kandidat Antimalaria

Abstract

Malaria remains a major global health problem due to the increasing resistance of Plasmodium falciparum to currently available antimalarial drugs. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), an essential enzyme in the de novo pyrimidine biosynthesis pathway, has emerged as a promising target for antimalarial drug discovery. This study aimed to evaluate the potential of five chalcone derivatives as antimalarial candidates using an in silico approach. The study employed molecular docking, binding pocket analysis, 200 ns molecular dynamics simulation, and ADMET prediction. The molecular docking results showed that all compounds occupied the same inhibitor binding pocket as the reference ligand DSM705, with binding affinity values ranging from −7.7 to −9.7 kcal/mol, while the reference ligand exhibited −10.9 kcal/mol. Molecular dynamics simulations demonstrated stable protein–ligand complexes based on protein RMSD, ligand RMSD, and RMSF analyses. ADMET prediction indicated favorable pharmacokinetic properties for all compounds, with Human Intestinal Absorption values above 91%, while the SCH3 derivative exhibited the most favorable toxicity profile. Overall, the five chalcone derivatives showed promising potential as PfDHODH inhibitor-based antimalarial candidates.