{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:03:30Z","timestamp":1753862610930,"version":"3.41.2"},"reference-count":60,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Schistosomiasis or bilharzia is caused by blood flukes of the genus <jats:italic>Schistosoma<\/jats:italic> and represents a considerable health and economic burden in tropical and subtropical regions. The treatment of this infectious disease relies on one single drug: praziquantel (PZQ). Therefore, new and potent antischistosomal compounds need to be developed. In our previous work, starting with the drug disulfiram, we developed dithiocarbamates with in vitro antischistosomal activities in the low micromolar range. Based on these results, we report in this study on the synthesis and biological testing of the structurally related dithiocarbazates against <jats:italic>Schistosoma mansoni<\/jats:italic>, one of the major species of schistosomes. In total, three series of dithiocarbazate derivatives were examined, and we found that the antischistosomal activity of <jats:italic>N<\/jats:italic>\u2010unbranched dithiocarbazates increased by further <jats:italic>N<\/jats:italic>\u2010substitution. Comparable tetra\u2010substituted dithiocarbazates were rarely described in the literature, thus a synthesis route was established. Due to the elaborate synthesis, the branched dithiocarbazates (containing an <jats:italic>N<\/jats:italic>\u2010aminopiperazine) were simplified, but the resulting branched dithiocarbamates (containing a 4\u2010aminopiperidine) were considerably less active. Taken together, dithiocarbazate\u2010containing compounds with an in vitro antischistosomal activity of 5\u2009\u00b5M were obtained.<\/jats:p>","DOI":"10.1002\/ardp.202200491","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T03:00:53Z","timestamp":1670554853000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["From dithiocarbamates to branched dithiocarbazates: Compounds with potent antischistosomal activity"],"prefix":"10.1002","volume":"356","author":[{"given":"Tom L.","family":"Gallinger","sequence":"first","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":"Kerstin","family":"Lange\u2010Gr\u00fcnweller","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Philipps University Marburg Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Schmidt","sequence":"additional","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":"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":[[2022,12,8]]},"reference":[{"unstructured":"WHO\u2010Fact Sheet Schistosomiasis https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/schistosomiasis(accessed: January 2022).","key":"e_1_2_7_2_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_3_1","DOI":"10.1021\/acsinfecdis.0c00542"},{"doi-asserted-by":"publisher","key":"e_1_2_7_4_1","DOI":"10.1007\/s00436-012-3151-z"},{"unstructured":"Ending the Neglect to Attain the Sustainable Development Goals \u2212 A Road Map for Neglected Tropical Diseases 2021\u22122030.World Health Organization:Geneva2020.","key":"e_1_2_7_5_1"},{"unstructured":"Press Release Merck KGaA Merck Announces Positive Phase III Results for Arpraziquantel as Part of Its Schistosomiasis Elimination Program https:\/\/www.merckgroup.com\/de\/news\/phase-three-results-for-arpraziquantel-16-11-2021.html(accessed:\u00a0 January 2022).","key":"e_1_2_7_6_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_7_1","DOI":"10.1007\/BF00389899"},{"doi-asserted-by":"publisher","key":"e_1_2_7_8_1","DOI":"10.1016\/j.ejmech.2022.114641"},{"doi-asserted-by":"publisher","key":"e_1_2_7_9_1","DOI":"10.1016\/j.jinorgbio.2010.08.009"},{"doi-asserted-by":"publisher","key":"e_1_2_7_10_1","DOI":"10.1016\/j.ejmech.2010.01.028"},{"doi-asserted-by":"publisher","key":"e_1_2_7_11_1","DOI":"10.1016\/j.bioorg.2020.103771"},{"doi-asserted-by":"publisher","key":"e_1_2_7_12_1","DOI":"10.1016\/S0223-5234(00)00145-8"},{"doi-asserted-by":"publisher","key":"e_1_2_7_13_1","DOI":"10.3906\/kim-2006-22"},{"doi-asserted-by":"publisher","key":"e_1_2_7_14_1","DOI":"10.1039\/c2dt12387h"},{"doi-asserted-by":"publisher","key":"e_1_2_7_15_1","DOI":"10.1016\/j.jinorgbio.2020.111331"},{"doi-asserted-by":"publisher","key":"e_1_2_7_16_1","DOI":"10.1021\/acs.jmedchem.0c01936"},{"doi-asserted-by":"publisher","key":"e_1_2_7_17_1","DOI":"10.1016\/0014-5793(77)80276-7"},{"doi-asserted-by":"publisher","key":"e_1_2_7_18_1","DOI":"10.1021\/jm00204a018"},{"doi-asserted-by":"publisher","key":"e_1_2_7_19_1","DOI":"10.1016\/j.bmcl.2014.10.040"},{"doi-asserted-by":"publisher","key":"e_1_2_7_20_1","DOI":"10.1039\/b010091a"},{"doi-asserted-by":"publisher","key":"e_1_2_7_21_1","DOI":"10.1021\/ol0620141"},{"unstructured":"J. K.Choi I. B.Jhung J. C.Lee J. S.Sa S. J.Jo J. H.Cho(Lucky Ltd.) US 5405965 1995.","key":"e_1_2_7_22_1"},{"unstructured":"T. R.Hopkins J. R.Thornton J. R.Epperly(Gulf Oil Corporation) US 3395234 1968.","key":"e_1_2_7_23_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_24_1","DOI":"10.3184\/030823409X450453"},{"doi-asserted-by":"publisher","key":"e_1_2_7_25_1","DOI":"10.1016\/S0040-4039(99)02286-8"},{"doi-asserted-by":"publisher","key":"e_1_2_7_26_1","DOI":"10.1021\/jo000487u"},{"doi-asserted-by":"publisher","key":"e_1_2_7_27_1","DOI":"10.1080\/00397910600602735"},{"doi-asserted-by":"publisher","key":"e_1_2_7_28_1","DOI":"10.1007\/s00706-011-0572-9"},{"doi-asserted-by":"publisher","key":"e_1_2_7_29_1","DOI":"10.1007\/s00706-011-0708-y"},{"key":"e_1_2_7_30_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1107\/S010876731104774X","volume":"68","author":"Szczesio M.","year":"2012","journal-title":"Acta Crystallogr. Sect. C: Cryst. Struct. Commun."},{"doi-asserted-by":"publisher","key":"e_1_2_7_31_1","DOI":"10.1016\/j.poly.2007.05.039"},{"doi-asserted-by":"publisher","key":"e_1_2_7_32_1","DOI":"10.1016\/0022-1902(77)80202-9"},{"unstructured":"M. G.Bock H.Moebitz S. K.Panigrahi R.Podutoori S.Samajdar(Novartis AG) WO 2015\/022663 2015.","key":"e_1_2_7_33_1"},{"unstructured":"Y.Moritani R.Imashiro A.Sato(Tanabe Seiyku Co. Ltd.) WO 2007\/046550 2007.","key":"e_1_2_7_34_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_35_1","DOI":"10.1016\/j.tet.2005.05.056"},{"doi-asserted-by":"publisher","key":"e_1_2_7_36_1","DOI":"10.1016\/j.tet.2011.11.091"},{"doi-asserted-by":"publisher","key":"e_1_2_7_37_1","DOI":"10.1002\/jhet.5570380310"},{"doi-asserted-by":"publisher","key":"e_1_2_7_38_1","DOI":"10.1002\/cctc.202001537"},{"doi-asserted-by":"publisher","key":"e_1_2_7_39_1","DOI":"10.1055\/s-0030-1261170"},{"doi-asserted-by":"publisher","key":"e_1_2_7_40_1","DOI":"10.1080\/00397910903007111"},{"unstructured":"I.Shima K.Ohne(Fujisawa Pharmaceuticals Co. Ltd.) US 6291464 2001.","key":"e_1_2_7_41_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_42_1","DOI":"10.1016\/j.bmc.2008.07.062"},{"doi-asserted-by":"publisher","key":"e_1_2_7_43_1","DOI":"10.1080\/10426507.2012.723653"},{"unstructured":"T. L.Riss R. A.Moravec A. L.Niles S.Duellman H. A.Benink T. J.Worzella L.MinorCell Viability Assays Eli Lilly & Company and the National Center for advancing translational Sciences Bethesda 2013.","key":"e_1_2_7_44_1"},{"doi-asserted-by":"publisher","key":"e_1_2_7_45_1","DOI":"10.1002\/jhet.5570270739"},{"doi-asserted-by":"publisher","key":"e_1_2_7_46_1","DOI":"10.1021\/jm100432w"},{"doi-asserted-by":"publisher","key":"e_1_2_7_47_1","DOI":"10.1002\/ajoc.201700481"},{"doi-asserted-by":"publisher","key":"e_1_2_7_48_1","DOI":"10.1002\/cmdc.200700112"},{"doi-asserted-by":"publisher","key":"e_1_2_7_49_1","DOI":"10.1016\/j.ejmech.2011.03.033"},{"doi-asserted-by":"publisher","key":"e_1_2_7_50_1","DOI":"10.1002\/ejoc.201700974"},{"doi-asserted-by":"publisher","key":"e_1_2_7_51_1","DOI":"10.1021\/jo1018816"},{"doi-asserted-by":"publisher","key":"e_1_2_7_52_1","DOI":"10.1021\/jo301372y"},{"doi-asserted-by":"crossref","unstructured":"J.Antel M.Firnges U.Schoen H.Waldeck M.Wurl D.Reiche G.Peter\u2010Colin(Solvay Pharmaceuticals GmbH) US 2007\/0149512 2007.","key":"e_1_2_7_53_1","DOI":"10.3833\/pdr.v2007i79.407"},{"doi-asserted-by":"publisher","key":"e_1_2_7_54_1","DOI":"10.1021\/jo0056343"},{"doi-asserted-by":"publisher","key":"e_1_2_7_55_1","DOI":"10.1021\/acs.jmedchem.5b01254"},{"doi-asserted-by":"publisher","key":"e_1_2_7_56_1","DOI":"10.1002\/cmdc.201600127"},{"doi-asserted-by":"publisher","key":"e_1_2_7_57_1","DOI":"10.1002\/ardp.202100259"},{"doi-asserted-by":"publisher","key":"e_1_2_7_58_1","DOI":"10.1002\/cmdc.201900423"},{"doi-asserted-by":"publisher","key":"e_1_2_7_59_1","DOI":"10.1007\/BF00930846"},{"doi-asserted-by":"publisher","key":"e_1_2_7_60_1","DOI":"10.1517\/17460441.2.S1.S53"},{"doi-asserted-by":"publisher","key":"e_1_2_7_61_1","DOI":"10.1038\/s41596-018-0101-y"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202200491","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.202200491","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202200491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T15:39:30Z","timestamp":1692373170000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202200491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":60,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/ardp.202200491"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202200491","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"type":"print","value":"0365-6233"},{"type":"electronic","value":"1521-4184"}],"subject":[],"published":{"date-parts":[[2022,12,8]]},"assertion":[{"value":"2022-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2200491"}}