Screening North American Plant Extracts Against Trypanosoma brucei, a Causative Agent for Sleeping Sickness

Human African Trypanosomiasis (HAT), sleeping sickness, is a protozoan parasitic disease caused by Trypanosoma brucei. The disease is endemic in regions of sub-Saharan Africa, covering 36 countries with more than 60 million people at risk. There are only a few drugs that are available for the treatment of HAT. Current therapies for HAT suffer from severe toxicities and require intramuscular or intravenous administrations. This situation is further aggravated due to the emergence of drug resistant variants. There is an urgent need for new drugs that can be effective orally against both stages of HAT. Natural products offer an unmatched source for bioactive molecules with new chemotypes. Extracts prepared from more than 500 plants collected from various parts of the North America were screened in vitro against blood stage forms of T. brucei. A significantly high number (153) of extracts showed >90% inhibition in proliferation of trypomastigote forms of T. brucei at 20µg/mL concentration. Active extracts were screened at concentrations ranging from 10–0.4µg/mL. Eight plant extracts were identified as potent antitrypanosomal extracts with IC₅₀ values <1µg/mL. Antitrypanosomal activity of these plants extracts was selective as none of these were significantly active against Leishmania donovani, Plasmodium falciparum or transformed THP1 human macrophage cells. Four additional plant extracts with IC₅₀'s of <2 and >1mg/ml also represented new antitrypanosomal leads. Further evaluation of these extracts is likely to yield new antitrypanosomal drug leads.