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Molecules 2017, 22(10), 1715; doi:10.3390/molecules22101715

Screening a Natural Product-Based Library against Kinetoplastid Parasites

1
Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia
2
Natural Product Chemistry, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia
*
Author to whom correspondence should be addressed.
Received: 5 September 2017 / Revised: 4 October 2017 / Accepted: 4 October 2017 / Published: 12 October 2017
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
View Full-Text   |   Download PDF [1923 KB, uploaded 13 October 2017]   |  

Abstract

Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC50 values of the natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC50 values of ≤ 10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC50 values < 5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified. View Full-Text
Keywords: natural products; kinetoplastids; neglected tropical disease; drug discovery; leishmaniasis; human African trypanosomiasis; Chagas disease natural products; kinetoplastids; neglected tropical disease; drug discovery; leishmaniasis; human African trypanosomiasis; Chagas disease
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zulfiqar, B.; Jones, A.J.; Sykes, M.L.; Shelper, T.B.; Davis, R.A.; Avery, V.M. Screening a Natural Product-Based Library against Kinetoplastid Parasites. Molecules 2017, 22, 1715.

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