{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T23:26:58Z","timestamp":1787182018227,"version":"build-2736575974"},"reference-count":73,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01AI151639"],"award-info":[{"award-number":["R01AI151639"]}]},{"name":"National Institutes of Health","award":["R21AI146460"],"award-info":[{"award-number":["R21AI146460"]}]},{"name":"National Institutes of Health","award":["R21AI156554"],"award-info":[{"award-number":["R21AI156554"]}]},{"name":"National Institutes of Health","award":["International Research Support Initiative Program (IRSIP)"],"award-info":[{"award-number":["International Research Support Initiative Program (IRSIP)"]}]},{"DOI":"10.13039\/501100004681","name":"Higher Education Commission","doi-asserted-by":"publisher","award":["R01AI151639"],"award-info":[{"award-number":["R01AI151639"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004681","name":"Higher Education Commission","doi-asserted-by":"publisher","award":["R21AI146460"],"award-info":[{"award-number":["R21AI146460"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004681","name":"Higher Education Commission","doi-asserted-by":"publisher","award":["R21AI156554"],"award-info":[{"award-number":["R21AI156554"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004681","name":"Higher Education Commission","doi-asserted-by":"publisher","award":["International Research Support Initiative Program (IRSIP)"],"award-info":[{"award-number":["International Research Support Initiative Program (IRSIP)"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Metals have been used in medicine since ancient times for the treatment of different ailments with various elements such as iron, gold and arsenic. Metal complexes have also been reported to show antibiotic and antiparasitic activity. In this context, we tested the antiparasitic potential of 10 organotin (IV) derivatives from 4-(4-methoxyphenylamino)-4 oxobutanoic acid (MS26) against seven eukaryotic pathogens of medical importance: Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, Entamoeba histolytica, Giardia lamblia, Naegleria fowleri and Schistosoma mansoni. Among the compounds with and without antiparasitic activity, compound MS26Et3 stood out with a 50% effective concentration (EC50) of 0.21 and 0.19 \u00b5M against promastigotes and intracellular amastigotes of L. donovani, respectively, 0.24 \u00b5M against intracellular amastigotes of T. cruzi, 0.09 \u00b5M against T. brucei, 1.4 \u00b5M against N. fowleri and impaired adult S. mansoni viability at 1.25 \u00b5M. In terms of host\/pathogen selectivity, MS26Et3 demonstrated relatively mild cytotoxicity toward host cells with a 50% viability concentration of 4.87 \u00b5M against B10R cells (mouse monocyte cell line), 2.79 \u00b5M against C2C12 cells (mouse myoblast cell line) and 1.24 \u00b5M against HEK923 cells (human embryonic kidney cell line). The selectivity index supports this molecule as a therapeutic starting point for a broad spectrum antiparasitic alternative. Proteomic analysis of host cells infected with L. donovani after exposure to MS26Et3 showed a reduced expression of Rab7, which may affect the fusion of the endosome with the lysosome, and, consequently, impairing the differentiation of L. donovani to the amastigote form. Future studies to investigate the molecular target(s) and mechanism of action of MS26Et3 will support its chemical optimization.<\/jats:p>","DOI":"10.3390\/pathogens11121424","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T01:58:46Z","timestamp":1669600726000},"page":"1424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling Using Leishmania donovani"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4335-3300","authenticated-orcid":false,"given":"Obaid","family":"Hayat","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Chemical and Life Sciences, Abdul Wali Khan University, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4564-5799","authenticated-orcid":false,"given":"Nazif","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Chemical and Life Sciences, Abdul Wali Khan University, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-1284","authenticated-orcid":false,"given":"Muhammad","family":"Sirajuddin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Science and Technology, Bannu 28100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6510-2409","authenticated-orcid":false,"given":"Miriam A.","family":"Giardini","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0194-9157","authenticated-orcid":false,"given":"Jennifer V.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol R.","family":"Francisco","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie Uli","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Maurya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6623-6268","authenticated-orcid":false,"given":"Dominic","family":"McGrosso","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor R.","family":"Caffrey","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9294-3927","authenticated-orcid":false,"given":"Anjan","family":"Debnath","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9574-8174","authenticated-orcid":false,"given":"Jair L.","family":"Siqueira-Neto","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gielen, M., and Tiekink, E.R. 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