{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:29:42Z","timestamp":1772252982857,"version":"3.50.1"},"reference-count":133,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss Science National Foundation","doi-asserted-by":"publisher","award":["CRSII5-173718"],"award-info":[{"award-number":["CRSII5-173718"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss Science National Foundation","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>Aiming toward compounds with improved anti-Toxoplasma activity by exploiting the parasite auxotrophies, a library of nucleobase-tethered trithiolato-bridged dinuclear ruthenium(II)-arene conjugates was synthesized and evaluated. Structural features such as the type of nucleobase and linking unit were progressively modified. For comparison, diruthenium hybrids with other type of molecules were also synthesized and assessed. A total of 37 compounds (diruthenium conjugates and intermediates) were evaluated in a primary screening for in vitro activity against transgenic Toxoplasma gondii tachyzoites constitutively expressing \u03b2-galactosidase (T. gondii \u03b2-gal) at 0.1 and 1 \u00b5M. In parallel, the cytotoxicity in non-infected host cells (human foreskin fibroblasts, HFF) was determined by alamarBlue assay. Twenty compounds strongly impairing parasite proliferation with little effect on HFF viability were subjected to T. gondii \u03b2-gal half maximal inhibitory concentration determination (IC50) and their toxicity for HFF was assessed at 2.5 \u00b5M. Two promising compounds were identified: 14, ester conjugate with 9-(2-oxyethyl)adenine, and 36, a click conjugate bearing a 2-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl substituent, with IC50 values of 0.059 and 0.111 \u00b5M respectively, significantly lower compared to pyrimethamine standard (IC50 = 0.326 \u00b5M). Both 14 and 36 exhibited low toxicity against HFF when applied at 2.5 \u00b5M and are candidates for potential treatment options in a suitable in vivo model.<\/jats:p>","DOI":"10.3390\/molecules27238173","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T03:24:09Z","timestamp":1669260249000},"page":"8173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New Nucleic Base-Tethered Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Compounds: Synthesis and Antiparasitic Activity"],"prefix":"10.3390","volume":"27","author":[{"given":"Oksana","family":"Desiatkina","sequence":"first","affiliation":[{"name":"Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"M\u00f6sching","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoleta","family":"Anghel","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghalia","family":"Boubaker","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7831-6211","authenticated-orcid":false,"given":"Yosra","family":"Amdouni","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"},{"name":"Laboratoire de Parasitologie, Institution de la Recherche et de l\u2019Enseignement Sup\u00e9rieur Agricoles, Universit\u00e9 de la Manouba, \u00c9cole Nationale de M\u00e9decine V\u00e9t\u00e9rinaire de Sidi Thabet, Sidi Thabet 2020, Tunisia"}],"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, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2096-0618","authenticated-orcid":false,"given":"Julien","family":"Furrer","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"P\u0103unescu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Torgerson, P.R., Devleesschauwer, B., Praet, N., Speybroeck, N., Willingham, A.L., Kasuga, F., Rokni, M.B., Zhou, X.N., Fevre, E.M., and Sripa, B. 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