Computational Screening of Bioactive Compounds Targeting Dihydrofolate Reductase in Trypanosoma brucei for Inhibitory Activity

Background and Objective: Human African Trypanosomiasis is a vector-borne parasitic disease caused by Trypanosoma brucei that threatens the lives of about 60 million people globally. This condition has spread through 36 countries in Sub-Saharan Africa. The objective of this study was to assess the inhibitory potential of the bioactive compounds from plants reported for the treatment of trypanosomiasis against dihydrofolate reductase. Materials and Methods: The crystal structure of the protein was retrieved from the protein database (PDB). The structures of the phytoconstituents of the plants under study were retrieved from the PubChem database. Docking of the drug target and the phytoconstituents was carried out using PyRx software. The binding affinity energies of the compounds were assessed from docking, and their predicted pharmacokinetic and pharmacodynamic properties were assessed using DruLito and ADMETsar 2.0. Results: Some of the bioactive compounds present in Tridax procumbens, and Annona senegalensis were able to interact with the drug target with sufficient binding affinity energies (>7.4 kcal/mol), while those of Allium sativum did not bind with sufficient energy (<7.5 kcal.mol) to the drug target, and therefore did not show promise as a potential inhibitor of the drug target. Conclusion: The selected bioactive compounds present in Tridax procumbens, and Annona senegalensis have the potential to inhibit the drug target in the parasite Trypanosoma brucei and should be investigated further.