Background: The parasitic protozoal infections leishmaniasis, human African
trypanosomiasis, and Chagas disease are neglected tropical diseases that pose serious health risks
for much of the world’s population. Current treatment options suffer from limitations, but plantderived
natural products may provide economically advantageous therapeutic alternatives. Several
germacranolide sesquiterpenoids have shown promising antiparasitic activities, but the
mechanisms of activity have not been clearly established.
Objective: The objective is to use in silico screening of known antiparasitic germacranolides
against recognized protozoal protein targets in order to provide insight into the molecular
mechanisms of activity of these natural products.
Methods: Conformational analyses of the germacranolides were carried out using density
functional theory, followed by molecular docking. A total of 88 Leishmania protein structures, 86
T. brucei protein structures, and 50 T. cruzi protein structures were screened against 27
Results: The in-silico screening has revealed which of the protein targets of Leishmania spp.,
Trypanosoma brucei, and Trypanosoma cruzi are preferred by the sesquiterpenoid ligands.