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Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene\u2010containing (Fc\u2010CH\n                    <jats:sub>2<\/jats:sub>\n                    \u2010OXA), ruthenocene\u2010containing (Rc\u2010CH\n                    <jats:sub>2<\/jats:sub>\n                    \u2010OXA) and benzene\u2010containing (Ph\u2010CH\n                    <jats:sub>2<\/jats:sub>\n                    \u2010OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    larvae and adult worms and\n                    <jats:italic>S. haematobium<\/jats:italic>\n                    adult worms, and were also active in vivo against adult\n                    <jats:italic>S. mansoni<\/jats:italic>\n                    . Encouraged by these promising results, we conducted additional in\u2010depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on\n                    <jats:italic>S. haematobium<\/jats:italic>\n                    and juvenile\n                    <jats:italic>S. mansoni<\/jats:italic>\n                    , computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on\n                    <jats:italic>S. haematobium<\/jats:italic>\n                    . This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.\n                  <\/jats:p>","DOI":"10.1002\/chem.202002856","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T15:18:51Z","timestamp":1599059931000},"page":"15232-15241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis**"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1985-0676","authenticated-orcid":false,"given":"Valentin","family":"Buchter","sequence":"first","affiliation":[{"name":"Swiss Tropical and Public Health Institute  Socinstrasse 57, P.O. box 4002 Basel Switzerland"},{"name":"University of Basel  Petersplatz 1, P.O. 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