Integrative Network Pharmacology and Molecular Docking of Phytochemicals of Fatuoa pilosa in Targeting Falcipain-3 for Malaria Therapy

Malaria remains a global health concern due to drug resistance in Plasmodium falciparum, prompting the search for novel therapies. Fatoua pilosa, a traditional medicinal plant from Timor Island Indonesia, has shown potential antimalarial activity. This research explores the antimalarial potential of F. pilosa by applying an integrative in silico approach that incorporates network pharmacology and molecular docking analyses. Nineteen bioactive compounds identified from F. pilosa were analyzed for pharmacological targets using SEA and SwissTargetPrediction, while malaria-related genes were sourced from OMIM, GeneCards, and DisGeNET. Protein–protein interaction (PPI) networks, pathway enrichment, and docking simulations with Falcipain-3 (FP3) were conducted to identify key molecular interactions. A total of 468 overlapping targets were identified between F. pilosa compounds and malaria-related genes. Network analysis highlighted STAT3 as a central node, with enrichment in immune-related pathways (e.g., MAPK cascade). ADME and toxicity analysis via SwissADME and ProTox-III revealed favorable drug-like properties in most compounds. Molecular docking indicated that cycloartenol (M9) exhibited strong binding affinity to FP3 (Vina score: –10.1 kcal/mol), comparable to the native ligand. The identified targets and pathways suggest that F. pilosa compounds may exert antimalarial effects through immune modulation and inhibition of hemoglobin-degrading enzymes. Cycloartenol (M9), in particular, shows promise as an FP3 inhibitor with acceptable pharmacokinetic and safety profiles. This study supports the antimalarial potential of F. pilosa, especially cycloartenol, as a promising candidate for further experimental validation and drug development against P. falciparum.