Computational Insights into the Antimalarial Potential of Geranylated Chalcone from <i>Terminalia brownii</i>: A Multi-target Approach Against <i>Plasmodium Falciparum</i> Enzymes

The emergence of resistance to existing antimalarial therapies has escalated the urgency for novel compounds that effectively inhibit <i>Plasmodium falciparum</i>. This comprehensive study explores the antimalarial potential of Geranylated Chalcone, a bioactive compound extracted from <i>Terminalia brownii</i>. The molecular structure of Geranylated Chalcone was generated and optimized using ChemDraw and Spartan14 software, respectively, and evaluated its theoretical bioavailability and toxicity profiles through the SwissADME web platform and ProTox 3.0 tool. Molecular docking studies was performed with AutoDock Vina to assess binding interactions with critical enzymes, including Falcipain-2, Falcipain-3, Plasmepsin-2, and Aminopeptidase. Geranylated Chalcone displayed notable binding affinities ranging from -6.4 to -7.3 kcal/mol, indicating substantial interactions facilitated by hydrogen bonds, van der Waals forces, and pi interactions. Furthermore, the compound demonstrated a favorable drug-likeness profile, adhering to Lipinski's rule of five and exhibiting low toxicity (LD<sub>50</sub>: 2652mg/kg). These findings substantiate that Geranylated Chalcone serves as a promising candidate for antimalarial drug development, possessing advantageous binding affinities and a multi-target profile. Elucidation of its therapeutic efficacy, in vitro and in vivo studies are essential to validate its potentiality as a groundbreaking antimalarial agent. This research contributes valuable insights into the multifaceted role of natural compounds in combating malaria and the pressing challenge of drug resistance.