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Dipeptidyl enoates were screened against rhodesain and human cathepsins\u2005B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (<jats:italic>S<\/jats:italic>,<jats:italic>E<\/jats:italic>)\u2010ethyl 5\u2010((<jats:italic>S<\/jats:italic>)\u20102\u2010{[(benzyloxy)carbonyl]amino}\u20103\u2010phenylpropanamido)\u20107\u2010methyl\u20104\u2010oxooct\u20102\u2010enoate (<jats:bold>6<\/jats:bold>) was the most potent, with an IC<jats:sub>50<\/jats:sub> value of 16.4\u2005n<jats:sc>M<\/jats:sc> and <jats:italic>k<\/jats:italic><jats:sub>inact<\/jats:sub>\/<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>=1.6\u00d710<jats:sup>6<\/jats:sup>\u2009<jats:sc>M<\/jats:sc><jats:sup>\u22121<\/jats:sup>\u2009s<jats:sup>\u22121<\/jats:sup> against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition kinetics data, supported by docking studies, suggest a dual mode of action via attack of cysteine thiolate at two reactive positions.<\/jats:p>","DOI":"10.1002\/cmdc.201500204","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T05:17:04Z","timestamp":1437023824000},"page":"1484-1487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action"],"prefix":"10.1002","volume":"10","author":[{"given":"Santiago","family":"Royo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Schirmeister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Kesselring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florenci V.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"e_1_2_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2004.01.004"},{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14694-6"},{"key":"e_1_2_4_3_2","unstructured":"\u00a0"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-1-3"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60829-1"},{"key":"e_1_2_4_6_2","unstructured":"Trypanosomiasis human African (sleeping sickness) World Health Organization (WHO) Fact Sheet #259 updated May 2015:www.who.int\/mediacentre\/factsheets\/fs259\/en\/."},{"key":"e_1_2_4_7_2","unstructured":"Center for Discovery and Innovation in Parasitic Diseases (CDIPD):www.cdipd.org\/index.php(accessed January 2015)."},{"key":"e_1_2_4_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000701"},{"key":"e_1_2_4_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm301424d"},{"key":"e_1_2_4_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00017a002"},{"key":"e_1_2_4_11_2","doi-asserted-by":"publisher","DOI":"10.1246\/cl.1984.1069"},{"key":"e_1_2_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.08.098"},{"key":"e_1_2_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.10.056"},{"key":"e_1_2_4_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_4_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.014340"},{"key":"e_1_2_4_16_2","unstructured":"In the docking studies the respective distances between the sulfur atom of Cys25 and the ketone carbonyl group C\u03b1 to the ketone and C\u03b1 to the ester in compound6are 4.664 4.153 and 4.504\u2005\u00c5."}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201500204","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201500204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:33:35Z","timestamp":1760265215000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201500204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,14]]},"references-count":16,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1002\/cmdc.201500204"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201500204","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,14]]},"assertion":[{"value":"2015-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}