@article{15578630585d43d6b7f0fd08355fb170,
title = "Temperate zone plant natural products—a novel resource for activity against tropical parasitic diseases",
abstract = "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{\textquoteright}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.",
keywords = "African trypanosomiasis, Drug discovery, Leishmaniasis, Malaria, Natural products, Neglected tropical diseases, Surra, Temperate zone",
author = "Hamza Hameed and King, {Elizabeth F.B.} and Katerina Doleckova and Barbara Bartholomew and Jackie Hollinshead and Haddijatou Mbye and Imran Ullah and Karen Walker and Veelen, {Maria Van} and Abou-Akkada, {Somaia Saif} and Nash, {Robert J.} and Horrocks, {Paul D.} and Price, {Helen P.}",
note = "Funding Information: This research was funded by the following sources: High Value Chemicals from Plants (BBSRC) to P.D.H., R.N., H.P.P.; Higher Committee for Education Development in Iraq (HCED) award (supporting H.H.); MRC grant MR/P011241/1 awarded to H.P.P. (supporting E.F.B.K.); British Council UK-Institutional Links Newton-Mosharafa Egypt grant number 261876735 awarded to H.P.P., S.S.A.A., P.D.H., R.J.N. (supporting K.D.); British Society for Antimicrobial Chemotherapy (BSAC) award BSAC-2018-0004 (supporting M.V.V.). We acknowledge Achim Schnaufer (University of Edinburgh) for providing the T. evansi, Lorna Maclean (University of Dundee) for providing the L. donovani strain and Alastair J. Durie for many helpful discussions around the chemical structures. Funding Information: Funding: This research was funded by the following sources: High Value Chemicals from Plants (BBSRC) to P.D.H., R.N., H.P.P.; Higher Committee for Education Development in Iraq (HCED) award (supporting H.H.); MRC grant MR/P011241/1 awarded to H.P.P. (supporting E.F.B.K.); British Council UK-Institutional Links Newton-Mosharafa Egypt grant number 261876735 awarded to H.P.P., S.S.A.A., P.D.H., R.J.N. (supporting K.D.); British Society for Antimicrobial Chemotherapy (BSAC) award BSAC-2018-0004 (supporting M.V.V.). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
month = mar,
day = "7",
doi = "10.3390/ph14030227",
language = "English",
volume = "14",
journal = "Pharmaceuticals",
publisher = "Multidisciplinary Digital Publishing Institute",
number = "3",
}
