Malaria is one of the most common diseases that threaten many of the subtropical and tropical regions. Countries where the risk of transmission of malaria is at the high rate are over a hundred currently and these counties are being visited by over 125, 000, 000 international travelers on yearly basis. Chemical structures of ligands were drawn with the MarvinSketch software and converted into SMILES strings for the calculation of pharmacokinetic parameters. The predicted binding energies between the three selected antifolate drugs, gedunin, its derivatives (C=O, C₂H₅, C₃H₆O₂, C₄H₈O₂, CONH₂, NH₂, OCH₃, OH) and the Plasmodium falciparium DHFR enzyme were -8.0, -7.5, -8.0, -9.5, -9.0, -8.4, -8.9, -8.2, -8.9, -8.7, -8.3, -8.4 Kcal/mol respectively. The results from the experiment showed that gedunin and its modified derivatives might be better antimalarial agents than the antifolate drugs as revealed by the predicted binding energies between the target enzyme and the ligands.