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Treatment heavily depends on limited drugs, together with drawbacks like toxicity and microbial resistance. The current research aimed to investigate in vitro growth inhibitory activity of Medicines for Malaria Ventures - Pathogen Box (MMV - PB) compounds against <jats:italic>L. aethiopica<\/jats:italic> clinical isolate.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methodology<\/jats:title>\n                <jats:p>Four hundred MMV \u2013 PB compounds were screened against <jats:italic>L. aethiopica<\/jats:italic> using resazurin based colourimetric assay. Compounds with &gt;\u200970% inhibition were further tested using macrophage based intracellular amastigote assay. Cytotoxic and hemolytic activity of candidate hits were assessed on THP1- cells and sheep red blood cells (RBCs), respectively. In vitro drug interaction study was also conducted for the most potent hit using the combination index method.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>At the test concentration of 1\u2009\u03bcM, twenty-three compounds showed &gt;\u200950% inhibition of promastigotes parasite growth, of which 11 compounds showed &gt;\u200970% inhibition. The 50% growth inhibition (IC<jats:sub>50<\/jats:sub>) of the 11 compounds was ranged from 0.024 to 0.483\u2009\u03bcM in anti-promastigote assay and from 0.064 to 0.899\u2009\u03bcM in intracellular amastigote assay. Candidate compounds demonstrated good safety on sheep RBCs and THP-1 cell lines. MMV688415 demonstrated a slight hemolytic activity on sheep RBC (5.3% at 25\u2009\u03bcM) and THP-1 cell line (CC<jats:sub>20<\/jats:sub>\u2009=\u200925\u2009\u03bcM) while MMV690102 inhibited half of THP-1 cells at 36.5\u2009\u03bcM (selectivity index\u2009=\u2009478). No synergistic activity was observed from the combinations of MMV690102 and amphotericin B (CI\u2009&gt;\u20091), and MMV690102 and Pentamidine (CI\u2009&gt;\u20091) at lower and higher combination points.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The present study identified a panel of compounds that can be used as a novel starting point for lead optimization. MMV690102 appears to be the most potent inhibitor against <jats:italic>L. aethiopica<\/jats:italic> promastigotes and amastigotes. Future works should investigate the antileishmanial mechanism of action and in vivo antileishmanial activities of identified hits.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40360-021-00538-2","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T12:02:58Z","timestamp":1637064178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In vitro growth inhibitory activity of Medicines for Malaria Venture pathogen box compounds against Leishmania aethiopica"],"prefix":"10.1186","volume":"22","author":[{"given":"Markos","family":"Tadele","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solomon M.","family":"Abay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Asaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyasu","family":"Makonnen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asrat","family":"Hailu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"issue":"9765","key":"538_CR1","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/S0140-6736(10)61495-X","volume":"377","author":"N Prasad","year":"2011","unstructured":"Prasad N, Ghiya BC, Bumb RA, Kaushal H, Saboskar AA, Lezama-davila CM, et al. 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Informed consent was obtained from the patient shortly after diagnosis which permits the use of the isolate for research purposes. Confidentiality and privacy kept by omitting the name of the patient. All procedures and techniques used in this study were per the national institute of health guidelines for the care and use of laboratory animals (Institute for Laboratory Animal Research, 2011) and following the ARRIVE Guidelines Checklist.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"There are no competing interests in this work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"71"}}