Temperate Zone Plant Natural Products—A Novel Resource for Activity against Tropical Parasitic Diseases
| Autor: | Maria Van Veelen, Imran Ullah, Robert J. Nash, Somaia Saif Abou-Akkada, Haddijatou Mbye, Karen Walker, Elizabeth F. B. King, Katerina Doleckova, Helen P. Price, Barbara Bartholomew, Hamza Hameed, Jackie Hollinshead, Paul Horrocks |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Surra S1 natural products malaria Pharmaceutical Science lcsh:Medicine lcsh:RS1-441 01 natural sciences Leishmania mexicana Article drug discovery lcsh:Pharmacy and materia medica 03 medical and health sciences Botany parasitic diseases medicine Parasite hosting neglected tropical diseases African trypanosomiasis leishmaniasis QR355 Miltefosine biology 010405 organic chemistry lcsh:R QK temperate zone Plasmodium falciparum Leishmaniasis Trypanosoma evansi biology.organism_classification medicine.disease Sterol 0104 chemical sciences QR 030104 developmental biology Molecular Medicine medicine.drug |
| Zdroj: | Pharmaceuticals Volume 14 Issue 3 Pharmaceuticals, Vol 14, Iss 227, p 227 (2021) |
| ISSN: | 1424-8247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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