{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:34:28Z","timestamp":1791221668418,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,12,8]],"date-time":"2011-12-08T00:00:00Z","timestamp":1323302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2012,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trypanothione synthetase (TryS) is essential for the survival of the protozoan parasite <jats:italic>Trypanosoma brucei<\/jats:italic>, which causes human African trypanosomiasis. It is one of only a handful of chemically validated targets for <jats:italic>T.\u2005brucei<\/jats:italic> in\u2005vivo. To identify novel inhibitors of <jats:italic>Tb<\/jats:italic>TryS we screened our in\u2010house diverse compound library that contains 62\u2009000 compounds. This resulted in the identification of six novel hit series of <jats:italic>Tb<\/jats:italic>TryS inhibitors. Herein we describe the SAR exploration of these hit series, which gave rise to one common series with potency against the enzyme target. Cellular studies on these inhibitors confirmed on\u2010target activity, and the compounds have proven to be very useful tools for further study of the trypanothione pathway in kinetoplastids.<\/jats:p>","DOI":"10.1002\/cmdc.201100420","type":"journal-article","created":{"date-parts":[[2011,12,8]],"date-time":"2011-12-08T16:25:49Z","timestamp":1323361549000},"page":"95-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Design, Synthesis and Biological Evaluation of <i>Trypanosoma brucei<\/i> Trypanothione Synthetase Inhibitors"],"prefix":"10.1002","volume":"7","author":[{"given":"Daniel","family":"Spinks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah S.","family":"Torrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin R.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Frearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Read","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan H.","family":"Fairlamb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Wyatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian H.","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,8]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33945"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2003.09.002"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(99)01414-3"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112181"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.46.100192.003403"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2003.062"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(03)00141-7"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612013397564"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3883489"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(03)00176-2"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2003.072"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01721.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303035200"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.02.008"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06761.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2007.08.019"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200900262"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801850200"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06670.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.045336"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(04)03069-7"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.10.010"},{"key":"e_1_2_6_23_2","unstructured":"M.Mochizuki S.Miura(Takeda Pharmaceutical Co. 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