{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:34:52Z","timestamp":1762299292731,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_184662"],"award-info":[{"award-number":["310030_184662"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>(1) Background: Neospora caninum is a major cause of abortion in cattle and represents a veterinary health problem of great economic significance. In order to identify novel chemotherapeutic agents for the treatment of neosporosis, the Medicines for Malaria Venture (MMV) Malaria Box, a unique collection of anti-malarial compounds, were screened against N. caninum tachyzoites, and the most efficient compounds were characterized in more detail. (2) Methods: A N. caninum beta-galactosidase reporter strain grown in human foreskin fibroblasts was treated with 390 compounds from the MMV Malaria Box. The IC50s of nine compounds were determined, all of which had been previously been shown to be active against another apicomplexan parasite, Theileria annulata. The effects of three of these compounds on the ultrastructure of N. caninum tachyzoites were further investigated by transmission electron microscopy at different timepoints after initiation of drug treatment. (3) Results: Five MMV Malaria Box compounds exhibited promising IC50s below 0.2 \u00b5M. The compound with the lowest IC50, namely 25 nM, was MMV665941. This compound and two others, MMV665807 and MMV009085, specifically induced distinct alterations in the tachyzoites. More specifically, aberrant structural changes were first observed in the parasite mitochondrion, and subsequently progressed to other cytoplasmic compartments of the tachyzoites. The pharmacokinetic (PK) data obtained in mice suggest that treatment with MMV665941 could be potentially useful for further in vivo studies. (4) Conclusions: We have identified five novel compounds with promising activities against N. caninum, the effects of three of these compounds were studies by transmission electron microscopy (TEM). Their modes of action are unknown and require further investigation.<\/jats:p>","DOI":"10.3390\/molecules25061460","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T05:55:16Z","timestamp":1585893316000},"page":"1460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In Vitro Activities of MMV Malaria Box Compounds against the Apicomplexan Parasite Neospora caninum, the Causative Agent of Neosporosis in Animals"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-9270","authenticated-orcid":false,"given":"Joachim","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Pathobiology, Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo A.","family":"Winzer","sequence":"additional","affiliation":[{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirandeep","family":"Samby","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture (MMV), 20, Route de Pr\u00e9-Bois, 1215 Geneva 15, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Hemphill","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Pathobiology, Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.meegid.2012.08.012","article-title":"A review of the infection, genetics, and evolution of Neospora caninum: From the past to the present","volume":"13","author":"Goodswen","year":"2013","journal-title":"Infect. 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