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The development of alternative treatment options is urgent, not only due to the threat of drug resistance, but also because the drawbacks of PZQ, such as its inactivity against juvenile stages, contribute to its incomplete cure rates, thus requiring repeated treatment. This study presents the design, synthesis, characterization, and biological evaluation of 10 novel organometallic derivatives of the old schistosomicide, niridazole. The in vitro characterization of the derivatives on different life stages of\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    showed that the activity profile of niridazole could be modified and extended. One ferrocenoyl derivative showed promising activity against all life cycle stages of\n                    <jats:italic>S. mansoni<\/jats:italic>\n                    . Two ferrocenyl and one ruthenocenyl derivatives also displayed higher potency against adult schistosomes than niridazole. In conclusion, valuable information could be gained on the structure\u2013activity relationship of the different organometallic modifications, which could be used to design a second generation of derivatives with further improved activity profiles.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500603","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T01:51:28Z","timestamp":1762307488000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multidisciplinary Preclinical Investigations on Ferrocenyl, Ruthenocenyl, and Benzyl Derivatives of Niridazole as New Drug Candidates against Schistosomiasis"],"prefix":"10.1002","volume":"20","author":[{"given":"Tanja","family":"Karpstein","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology Swiss Tropical and Public Health Institute  Kreuzstrasse 2 CH\u20104123 Allschwil 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