The use of plant-derived natural products for the treatment of tropical parasitic diseases often has ethnopharmacological origins. As such, plants grown in temperate regions remain largely untested for novel anti-parasitic activities. We describe here a screen of the PhytoQuest Phytopure library, a novel source comprising over 600 purified compounds from temperate zone plants, against in vitro culture systems for Plasmodium falciparum, Leishmania mexicana, Trypanosoma evansi and T. brucei. Initial screen revealed 6, 65, 15 and 18 compounds, respectively, that decreased each parasite's growth by at least 50% at 1-2 µM concentration. These initial hits were validated in concentration-response assays against the parasite and the human HepG2 cell line, identifying hits with EC50 < 1 μM and a selectivity index of >10. Two sesquiterpene glycosides were identified against P. falciparum, four sterols against L. mexicana, and five compounds of various scaffolds against T. brucei and T. evansi. An L. mexicana resistant line was generated for the sterol 700022, which was found to have cross-resistance to the anti-leishmanial drug miltefosine as well as to the other leishmanicidal sterols. This study highlights the potential of a temperate plant secondary metabolites as a novel source of natural products against tropical parasitic diseases.

Centre for Applied Entomology and Parasitology Keele University Staffordshire ST5 5BG UK

Department of Biology Faculty of Life Sciences University of Hradec Králové 500 03 Hradec Králové Czech Republic

Department of Chemistry College of Education for Pure Science University of Mosul Mosul Iraq

Faculty of Veterinary Medicine Alexandria University Alexandria Abis 10 Egypt

Harvard T H Chan School of Public Health Harvard University Boston MA 02115 USA

MRC Unit The Gambia at LSHTM Atlantic Boulevard Fajara Banjul PO Box 273 The Gambia

PhytoQuest Limited Aberystwyth SY23 3EB UK

School of Life Sciences Keele University Staffordshire ST5 5BG UK

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