{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:38:25Z","timestamp":1786977505327,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T00:00:00Z","timestamp":1389139200000},"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":[[2014,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A significant improvement in the treatment of trypanosomiases has been achieved with the recent development of nifurtimox\u2013eflornithine combination therapy (NECT). As an alternative to drug combinations and as a means to overcome most of the antitrypanosomatid drug discovery challenges, a multitarget drug design strategy has been envisaged. To begin testing this hypothesis, we designed and developed a series of quinone\u2013coumarin hybrids against glyceraldehyde\u20103\u2010phosphate dehydrogenase\/trypanothione reductase (GAPDH\/TR). These enzymes belong to metabolic pathways that are vital to\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    and\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    , and have thus been considered promising drug targets. The synthesized molecules were characterized for their dual\u2010target antitrypanosomal profile, both in enzyme assays and in in\u2005vitro parasite cultures. The merged derivative 2\u2010{[3\u2010(3\u2010dimethylaminopropoxy)\u20102\u2010oxo\u20102\n                    <jats:italic>H<\/jats:italic>\n                    \u2010chromen\u20107\u2010yl]oxy}anthracene\u20101,4\u2010dione (\n                    <jats:bold>10<\/jats:bold>\n                    ) showed an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 5.4\u2005\u03bc\n                    <jats:sc>M<\/jats:sc>\n                    against\n                    <jats:italic>Tb<\/jats:italic>\n                    GAPDH and a concomitant\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    value of 2.32\u2005\u03bc\n                    <jats:sc>M<\/jats:sc>\n                    against\n                    <jats:italic>Tc<\/jats:italic>\n                    TR. Notably, 2\u2010{4\u2010[6\u2010(2\u2010dimethylaminoethoxy)\u20102\u2010oxo\u20102\n                    <jats:italic>H<\/jats:italic>\n                    \u2010chromen\u20103\u2010yl]phenoxy}anthracene\u20101,4\u2010dione (compound\n                    <jats:bold>6<\/jats:bold>\n                    ) displayed a remarkable EC\n                    <jats:sub>50<\/jats:sub>\n                    value for\n                    <jats:italic>T.\u2005brucei<\/jats:italic>\n                    parasites (0.026\u2005\u03bc\n                    <jats:sc>M<\/jats:sc>\n                    ) combined with a very low cytotoxicity toward mammalian L6 cells (7.95\u2005\u03bc\n                    <jats:sc>M<\/jats:sc>\n                    ). This promising low toxicity of compound\n                    <jats:bold>6<\/jats:bold>\n                    might be at least partially due to the fact that it does not interfere with human glutathione reductase.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.201300399","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T16:43:55Z","timestamp":1389199435000},"page":"371-382","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Toward the Development of Dual\u2010Targeted Glyceraldehyde\u20103\u2010phosphate Dehydrogenase\/Trypanothione Reductase Inhibitors against\n                    <i>Trypanosoma brucei<\/i>\n                    and\n                    <i>Trypanosoma cruzi<\/i>"],"prefix":"10.1002","volume":"9","author":[{"given":"Federica","family":"Belluti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Uliassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Veronesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bergamini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Brun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Viola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"Fato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A. M.","family":"Michels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Luise","family":"Krauth\u2010Siegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cavalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Bolognesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,8]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14694-6"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70296-X"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70098-0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000718"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61117-X"},{"key":"e_1_2_6_6_2","unstructured":"\u00a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio837"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802611798184391"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2006.12.006"},{"key":"e_1_2_6_10_2","unstructured":"\u00a0"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9004835"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867311320130010"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867311320130004"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ml4000386"},{"key":"e_1_2_6_15_2","unstructured":"\u00a0"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527670383.ch9"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527670383.ch7"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/123702"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.08.019"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6051-9_11"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2008.03.006"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026023393048"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-002-0771-8"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.03.009"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002012"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm301112z"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200800396"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2007.05.088"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.08.102"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.04.060"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1467"},{"key":"e_1_2_6_32_2","unstructured":"\u00a0"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.08.002"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-010-0065-2"},{"key":"e_1_2_6_35_2","first-page":"963658","volume":"2012","author":"Santhosh K. V.","year":"2012","journal-title":"Sci. World J."},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02700-X"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2007.06.042"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm001079l"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200700172"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00264-6"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1824"},{"key":"e_1_2_6_42_2","unstructured":"RCSB Protein Data Bank http:\/\/pdb.org\/pdb\/home\/home.do(accessed December 13 2013)."},{"key":"e_1_2_6_43_2","unstructured":"Schr\u00f6dinger Suite 2010 Protein Preparation Wizard: Epik version 2.1 Impact version 5.6 and Prime version 2.2 Schr\u00f6dinger LLC New York NY (USA) 2010."},{"key":"e_1_2_6_44_2","unstructured":"LigPrep Schr\u00f6dinger LLC New York NY (USA) 2010."},{"key":"e_1_2_6_45_2","unstructured":"Glide Schr\u00f6dinger LLC New York NY (USA) 2010."},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.09.002"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(91)90231-T"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.05.002"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/md8010047"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201300399","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201300399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T16:56:21Z","timestamp":1760288181000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201300399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,8]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1002\/cmdc.201300399"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201300399","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,8]]},"assertion":[{"value":"2013-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}