Entamoeba histolytica
and
Giardia duodenalis
are widespread intestinal protozoan parasites which both spread via cysts that have to be ingested to infect a new host. Their environment, the small intestine for
G. duodenalis
and the colon for
E. histolytica
, contains only very limited amounts of oxygen, so both parasites generate energy by fermentation and substrate level phosphorylation rather than by oxidative phosphorylation. They both contain reducing agents able to reduce and activate nitroimidazole drugs such as metronidazole which is the gold standard drug to treat
Entamoeba
or
Giardia
infections. Although metronidazole works well in the majority of cases, it has a number of drawbacks. In animal models, the drug has carcinogenic activity, and concerns about a possible teratogenic activity remain. In addition, the treatment of
G. duodenalis
infections is hampered by emerging metronidazole resistance. Plant-derived drugs play a dominant role in human medicine, therefore we tested the activity of 14 isolated plant compounds belonging to seven different classes
in vitro
against both parasites. The tests were performed in a new setting in microtiter plates under anaerobic conditions. The compound with the highest activity was methylgerambullin, a sulphur-containing amide found in
Glycosmis
species of the family Rutaceae with an EC
50
of 14.5 μM (6.08 μg/ml) after 24 h treatment for
E. histolytica
and 14.6 μM (6.14 μg/ml) for
G. duodenalis
. The compound was successfully synthesised in the laboratory which opens the door for the generation of new derivatives with higher activity.
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