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This study evaluates eight novel 6-nitrocoumarin-3-thiosemicarbazone derivatives in an\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      human placenta model, assessing their antiparasitic activity and impact on tissue integrity. Two therapeutic approaches were tested: pre-infection (preventive) and post-infection (therapeutic).\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      assays revealed strong activity trends. Compound\n                      <jats:bold>7<\/jats:bold>\n                      was the most effective against\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      (IC\n                      <jats:sub>50<\/jats:sub>\n                      = 22.4 \u00b1 0.8 \u00b5M, logP = 2.49), while compound\n                      <jats:bold>1<\/jats:bold>\n                      exhibited the highest activity against\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      (IC\n                      <jats:sub>50<\/jats:sub>\n                      = 17.3 \u00b1 0.5 \u00b5M, logP = 1.44). Unlike current treatments, none of the compounds induced placental tissue damage, preserving trophoblast function. Structure-activity relationship (SAR) analysis identified an inverse correlation between lipophilicity and antiparasitic activity in\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      , where polar compounds were more effective. In\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      , higher lipophilicity favored trypanocidal activity, suggesting differential cell permeability mechanisms. Mechanistic studies using electrochemistry and electron spin resonance (ESR) demonstrated that nitro group bioreduction promotes ROS generation, explaining activity against\n                      <jats:italic toggle=\"yes\">T. cruzi<\/jats:italic>\n                      . By contrast, lower ROS levels in\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      suggest alternative mechanisms. This study validates the\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      human placenta model as a clinically relevant platform for antiparasitic drug screening. The findings highlight 6-nitrocoumarin-3-thiosemicarbazones as promising early-stage candidates that warrant further optimization to develop safer and more effective therapies for congenital infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00454-25","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T13:51:27Z","timestamp":1754574687000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["New derivatives of 6-nitrocoumarin-3-thiosemicarbazone exhibit improved antiparasitic activity in the placenta against\n                    <i>Trypanosoma cruzi<\/i>\n                    and\n                    <i>Toxoplasma gondii<\/i>"],"prefix":"10.1128","volume":"69","author":[{"given":"Esteban","family":"Rocha-Valderrama","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0481m0575","id-type":"ROR","asserted-by":"publisher"}],"name":"Instituto Universitario de Investigaci\u00f3n y Desarrollo Tecnol\u00f3gico, Universidad Tecnol\u00f3gica Metropolitana","place":["Santiago, Chile"]},{"id":[{"id":"https:\/\/ror.org\/047gc3g35","id-type":"ROR","asserted-by":"publisher"}],"name":"Inorganic and Analytical Department, Free Radical and Antioxidants Laboratory, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Rost\u00e1n","sequence":"additional","affiliation":[{"name":"\u00c1rea Qu\u00edmica Inorg\u00e1nica, DEC, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica","place":["Montevideo, Uruguay"]},{"name":"Graduate Program in Chemistry, Facultad de 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