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Modifications to positions 5 and 4\u2032 of the well\u2010known ENR inhibitor triclosan afforded a series of 29 new analogues. Among the resulting compounds, many showed high potency and improved physicochemical properties in comparison with the lead. The most potent compounds <jats:bold>16\u2009a<\/jats:bold> and <jats:bold>16\u2009c<\/jats:bold> have IC<jats:sub>50<\/jats:sub> values of 250\u2005n<jats:sc>M<\/jats:sc> against <jats:italic>Toxoplasma gondii<\/jats:italic> tachyzoites without apparent toxicity to the host cells. Their IC<jats:sub>50<\/jats:sub> values against recombinant <jats:italic>Tg<\/jats:italic>ENR were found to be 43 and 26\u2005n<jats:sc>M<\/jats:sc>, respectively. Additionally, 11 other analogues in this series had IC<jats:sub>50<\/jats:sub> values ranging from 17 to 130\u2005n<jats:sc>M<\/jats:sc> in the enzyme\u2010based assay. With respect to their excellent in\u2005vitro activity as well as improved drug\u2010like properties, the lead compounds <jats:bold>16\u2009a<\/jats:bold> and <jats:bold>16\u2009c<\/jats:bold> are deemed to be excellent starting points for the development of new medicines to effectively treat <jats:italic>Toxoplasma gondii<\/jats:italic> infections.<\/jats:p>","DOI":"10.1002\/cmdc.201300050","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T08:37:12Z","timestamp":1371199032000},"page":"1138-1160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Modification of Triclosan Scaffold in Search of Improved Inhibitors for Enoyl\u2010Acyl Carrier Protein (ACP) Reductase in <i>Toxoplasma gondii<\/i>"],"prefix":"10.1002","volume":"8","author":[{"given":"Jozef","family":"Stec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Fomovska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo A.","family":"Afanador","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Muench","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u2010Shiun","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"El\u2005Bissati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Hickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patty J.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Leed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Auschwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Sommervile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean T.","family":"Prigge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"McLeod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan P.","family":"Kozikowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,14]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(00)00124-7"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(01)02093-1"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/15.2.211"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-2-8178-0847-5_12"},{"key":"e_1_2_6_5_2","first-page":"51","volume":"119","author":"Roberts F.","year":"2001","journal-title":"Arch. 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