Evaluation of the Antitrypanosomal Activity of the Crude Extracts of Uvaria Ovata: In vitro and In silico Approach

Abstract

Background: Human African trypanosomiasis is the third disease with most mortalities among the neglected tropical diseases. The absence of vaccines and the development of parasite resistance have necessitated the quest for new affordable and safe treatment options for the disease. This study aims to assess the potential of Uvaria ovata as an alternative new and safer antitrypanosomal therapeutics. Methods: Antitrypanosomal efficacies of extracts and fractions of U. ovata were determined by the Alamar Blue cell viability assay against Trypanosoma brucei brucei GUTat 3.1. Molecular docking was used to suggest the mechanism of action of the extracts and fractions by docking the curated compounds present in the plant against farnesyl diphosphate synthase (FPPS) and ornithine decarboxylase (ODC) enzymes. Results: Antitrypanosomal activities (IC50, μg/mL) obtained were within the range of 0.12–4.40, exceeding that of the standard suramin (4.96). A total of 17 known compounds from U. ovata that did not violate Lipinski’s rule of five with negligible toxicity produced molecular docking results against FPPS and ODC enzymes. Within the FPPS interaction landscape, mannosamine emerged as the most promising lead, with a binding energy of −6.4 kcal/mol and a predicted Ki value of 20.12 μM. With respect to ODC, 15 compounds exhibited binding affinities ranging from −4.6 to −6.3 kcal/mol, exceeding that of the known inhibitor allicin (−4.5 kcal/mol). Conclusion: This is the first report of the antitrypanosomal activity and mode of action suggestion of U. ovata. The study sets the foundation for further exploration and validation of the therapeutic prospect of U. ovata in the fight against trypanosomiasis.

Keywords

• farnesyl diphosphate synthase
• molecular docking
• ornithine decarboxylase
• trypanosoma brucei brucei
• uvaria ovata