{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:43:39Z","timestamp":1760150619333,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["192072"],"award-info":[{"award-number":["192072"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"federal state Hessen of the Federal Republic of Germany","award":["192072"],"award-info":[{"award-number":["192072"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>The metacestode stage of the fox tapeworm Echinococcus multilocularis causes the severe zoonotic disease alveolar echinococcosis. New treatment options are urgently needed. Disulfiram and dithiocarbamates were previously shown to exhibit activity against the trematode Schistosoma mansoni. As both parasites belong to the platyhelminths, here we investigated whether these compounds were also active against E. multilocularis metacestode vesicles in vitro. We used an in vitro drug-screening cascade for the identification of novel compounds against E. multilocularis metacestode vesicles with disulfiram and 51 dithiocarbamates. Five compounds showed activity against E. multilocularis metacestode vesicles after five days of drug incubation in a damage marker release assay. Structure\u2013activity relationship analyses revealed that a S-2-hydroxy-5-nitro benzyl moiety was necessary for anti-echinococcal activity, as derivatives without this group had no effect on E. multilocularis metacestode vesicles. The five active compounds were further tested for potential cytotoxicity in mammalian cells. For two compounds with low toxicity (Schl-32.315 and Schl-33.652), IC50 values in metacestode vesicles and IC50 values in germinal layer cells were calculated. The compounds were not highly active on isolated GL cells with IC50 values of 27.0 \u00b1 4.2 \u00b5M for Schl-32.315 and 24.7 \u00b1 11.5 \u00b5M for Schl-33.652, respectively. Against metacestode vesicles, Schl-32.315 was not very active either with an IC50 value of 41.6 \u00b1 3.2 \u00b5M, while Schl-33.652 showed a low IC50 of 4.3 \u00b1 1 \u00b5M and should be further investigated in the future for its activity against alveolar echinococcosis.<\/jats:p>","DOI":"10.3390\/tropicalmed8120517","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T11:09:30Z","timestamp":1702379370000},"page":"517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Vitro Activities of Dithiocarbamate Derivatives against Echinococcus multilocularis Metacestode Vesicles"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-8517","authenticated-orcid":false,"given":"Marc","family":"Kaethner","sequence":"first","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Rennar","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Philipps-Universit\u00e4t Marburg, 35037 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Gallinger","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Philipps-Universit\u00e4t Marburg, 35037 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"K\u00e4mpfer","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0622-2128","authenticated-orcid":false,"given":"Andrew","family":"Hemphill","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"M\u00e4der","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Philipps-Universit\u00e4t Marburg, 35037 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0132-6577","authenticated-orcid":false,"given":"Ana","family":"Luque-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de S\u00edntesis Qu\u00edmica y Cat\u00e1lisis Homog\u00e9nea (ISQCH), Facultad de Ciencias, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Schlitzer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Philipps-Universit\u00e4t Marburg, 35037 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2672-5766","authenticated-orcid":false,"given":"Britta","family":"Lundstr\u00f6m-Stadelmann","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland"},{"name":"Multidisciplinary Center for Infectious Diseases, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1128\/CMR.17.1.107-135.2004","article-title":"Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern","volume":"17","author":"Eckert","year":"2004","journal-title":"Clin. 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