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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 \u2264 10 \u00b5M against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC50 values &lt; 5 \u00b5M. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified.<\/jats:p>","DOI":"10.3390\/molecules22101715","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T13:06:19Z","timestamp":1507813579000},"page":"1715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Screening a Natural Product-Based Library against Kinetoplastid Parasites"],"prefix":"10.3390","volume":"22","author":[{"given":"Bilal","family":"Zulfiqar","sequence":"first","affiliation":[{"name":"Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Jones","sequence":"additional","affiliation":[{"name":"Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Sykes","sequence":"additional","affiliation":[{"name":"Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Shelper","sequence":"additional","affiliation":[{"name":"Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4291-7573","authenticated-orcid":false,"given":"Rohan","family":"Davis","sequence":"additional","affiliation":[{"name":"Natural Product Chemistry, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-2299","authenticated-orcid":false,"given":"Vicky","family":"Avery","sequence":"additional","affiliation":[{"name":"Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,12]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2015). 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