{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T17:49:21Z","timestamp":1759340961702,"version":"3.41.2"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHL 383\/6\u20101 and GR1549\/10\u20101"],"award-info":[{"award-number":["SCHL 383\/6\u20101 and GR1549\/10\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus <jats:italic>Schistosoma<\/jats:italic> and causes severe morbidity in infected patients. In 2018, 290.8 million people required treatment, and 200,000 deaths are reported per year. Treatment of this disease depends on a single drug, praziquantel (PZQ). However, in the past few years, reduced sensitivity of the parasites toward PZQ has been reported. Therefore, there is an urgent need for new drugs against this disease. In the past few years, we have focused on a new substance class called biaryl alkyl carboxylic acid derivatives, which showed promising antischistosomal activity in vitro. Structure\u2013activity relationship (SAR) studies of the carboxylic acid moiety led to three promising carboxylic amides (morpholine, thiomorpholine, and methyl sulfonyl piperazine) with an antischistosomal activity down to 10\u2009\u00b5M (morpholine derivative) and no cytotoxicity up to 100\u2009\u00b5M. Here, we show our continued work on this substance class. We investigated, in extended SAR studies, whether modification of the linker and the thiophene ring could improve the antischistosomal activity. We found that the exchange of the alkyl linker by a pentadienyl or benzyl linker was tolerated and led to similar antischistosomal effects, whereas the exchange of the thiophene ring was not tolerated. Our data suggest that the thiophene ring is important for the antischistosomal activity of this compound class.<\/jats:p>","DOI":"10.1002\/ardp.202100259","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T11:07:31Z","timestamp":1631704051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synthesis and antischistosomal activity of linker\u2010 and thiophene\u2010modified biaryl alkyl carboxylic acid derivatives"],"prefix":"10.1002","volume":"354","author":[{"given":"Alejandra M.","family":"Peter Ventura","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University Marburg Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Haeberlein","sequence":"additional","affiliation":[{"name":"BFS, Institute of Parasitology Justus Liebig University Giessen Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Konopka","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University Marburg Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Obermann","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University Marburg Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold","family":"Gr\u00fcnweller","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University Marburg Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph G.","family":"Grevelding","sequence":"additional","affiliation":[{"name":"BFS, Institute of Parasitology Justus Liebig University Giessen Giessen 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":"Institute of Pharmaceutical Chemistry Philipps University Marburg Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_7_2_1","DOI":"10.1016\/j.ijid.2014.07.009"},{"key":"e_1_2_7_3_1","first-page":"749","volume":"92","author":"WHO","year":"2017","journal-title":"Weekly Epidemiological Record (Relev\u00e9 \u00c9pid\u00e9miologique Hebdomadaire)"},{"doi-asserted-by":"publisher","key":"e_1_2_7_4_1","DOI":"10.1002\/cmdc.201800572"},{"unstructured":"WHO Schistosomiasis https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/schistosomiasis(accessed: July2021).","key":"e_1_2_7_5_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_6_1","DOI":"10.1002\/anie.201208390"},{"doi-asserted-by":"publisher","key":"e_1_2_7_7_1","DOI":"10.4269\/ajtmh.1994.51.83"},{"doi-asserted-by":"publisher","key":"e_1_2_7_8_1","DOI":"10.1517\/17460441.2.S1.S35"},{"doi-asserted-by":"publisher","key":"e_1_2_7_9_1","DOI":"10.1002\/cmdc.201600127"},{"doi-asserted-by":"publisher","key":"e_1_2_7_10_1","DOI":"10.1007\/s00436-016-5146-7"},{"doi-asserted-by":"publisher","key":"e_1_2_7_11_1","DOI":"10.1002\/cmdc.201900423"},{"doi-asserted-by":"publisher","key":"e_1_2_7_12_1","DOI":"10.1016\/S0166-6851(02)00031-2"},{"doi-asserted-by":"publisher","key":"e_1_2_7_13_1","DOI":"10.1016\/j.cbi.2011.02.023"},{"doi-asserted-by":"publisher","key":"e_1_2_7_14_1","DOI":"10.1016\/j.ijpara.2010.01.007"},{"unstructured":"A. M.Peter Ventura Thesis Philipps\u2010Universit\u00e4t Marburg 2020.","key":"e_1_2_7_15_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_16_1","DOI":"10.1016\/j.tetlet.2013.04.110"},{"doi-asserted-by":"publisher","key":"e_1_2_7_17_1","DOI":"10.1002\/ejoc.200300400"},{"doi-asserted-by":"publisher","key":"e_1_2_7_18_1","DOI":"10.1111\/cbdd.12658"},{"doi-asserted-by":"publisher","key":"e_1_2_7_19_1","DOI":"10.1002\/jhet.2422"},{"doi-asserted-by":"publisher","key":"e_1_2_7_20_1","DOI":"10.1007\/s00706-003-0114-1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_21_1","DOI":"10.1016\/j.bmc.2011.09.031"},{"doi-asserted-by":"publisher","key":"e_1_2_7_22_1","DOI":"10.1007\/s00044-012-0382-6"},{"doi-asserted-by":"publisher","key":"e_1_2_7_23_1","DOI":"10.1007\/BF00930846"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202100259","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.202100259","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202100259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:45:26Z","timestamp":1693197926000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202100259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":22,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/ardp.202100259"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202100259","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"type":"print","value":"0365-6233"},{"type":"electronic","value":"1521-4184"}],"subject":[],"published":{"date-parts":[[2021,9,15]]},"assertion":[{"value":"2021-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2100259"}}