In silico discovery of new ornithine decarboxylase inhibitor with potential for human African trypanosomiasis treatment

Human African trypanosomiasis (HAT), a neglected tropical disease endemic to sub-Saharan Africa, faces treatment challenges due to drug-resistant Trypanosoma brucei strains and the need for safer and more effective therapeutic options. This study employed computational approaches, including 3D-similarity search, ADMET predictions, molecular docking simulation, and molecular dynamics (MD) simulation, to identify potential ornithine decarboxylase (ODC) inhibitors. Screening ChEMBL, DrugBank, and ZINC databases yielded seven eflornithine analogues as initial hit candidates. Structural optimization of these hit candidates led to the discovery of a novel compound with improved binding affinity, ADMET properties, safety profiles, and medicinal chemistry friendliness. MD simulation confirmed the stability of the protein–ligand complex involving ODC and the new compound. This study identifies the new compound as a promising candidate for the development of alternative ODC inhibitors for HAT treatment.