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The risk of the emergence of resistant schistosomes is known to be increasing, as a reduced sensitivity of these parasites toward praziquantel has been observed. We developed a new class of substances, which are derived from inhibitors of human aldose reductase, and which showed promising activity against <jats:italic>Schistosoma mansoni<\/jats:italic> couples in\u2005vitro. Further optimisation of the compounds led to an increase in anti\u2010schistosomal activity with observed phenotypes such as reduced egg production, vitality, and motility as well as tegumental damage and gut dilatation. Here, we performed structure\u2013activity relationship studies on the carboxylic acid moiety of biarylalkyl carboxylic acids. Out of 82 carboxylic acid amides, we identified 10 compounds that are active against <jats:italic>S. mansoni<\/jats:italic> at 25\u2005\u03bc<jats:sc>m<\/jats:sc>. The best five compounds showed an anti\u2010schistosomal activity up to 10\u2005\u03bc<jats:sc>m<\/jats:sc> and induced severe phenotypes. Cytotoxicity tests in human cell lines showed that two derivatives had no cytotoxicity at 50 or 100\u2005\u03bc<jats:sc>m<\/jats:sc>. These compounds are promising candidates for further optimisation toward the new anti\u2010schistosomal agents.<\/jats:p>","DOI":"10.1002\/cmdc.201900423","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T12:37:37Z","timestamp":1566909457000},"page":"1856-1862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development of Biarylalkyl Carboxylic Acid Amides with Improved Anti\u2010schistosomal Activity"],"prefix":"10.1002","volume":"14","author":[{"given":"Alejandra M.","family":"Peter Ventura","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Philipps Universit\u00e4t Marburg  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Haeberlein","sequence":"additional","affiliation":[{"name":"BFS, Institute of Parasitology Justus-Liebig-Universit\u00e4t Gie\u00dfen  Schubertstrasse 81 35392 Gie\u00dfen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Lange\u2010Gr\u00fcnweller","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Philipps Universit\u00e4t Marburg  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold","family":"Gr\u00fcnweller","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Philipps Universit\u00e4t Marburg  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland K.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Philipps Universit\u00e4t Marburg  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph G.","family":"Grevelding","sequence":"additional","affiliation":[{"name":"BFS, Institute of Parasitology Justus-Liebig-Universit\u00e4t Gie\u00dfen  Schubertstrasse 81 35392 Gie\u00dfen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-6273","authenticated-orcid":false,"given":"Martin","family":"Schlitzer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Philipps Universit\u00e4t Marburg  Marbacher Weg 6 35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"World Health Organization Weekly Epidemiological Record 2017 92 749\u2013760."},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800572"},{"key":"e_1_2_7_3_1","unstructured":"World Health Organization Schistosomiasis:https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/schistosomiasis 2018 (accessed June 2019)."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1994.50.281"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69440-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2014.07.009"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201208390"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201208390"},{"key":"e_1_2_7_8_1","first-page":"190","volume":"81","author":"Ferrari M. 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