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Considering that irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael\u2010acceptor was introduced as the warhead; this portion was functionalized in order to evaluate the size of corresponding enzyme pocket that could accommodate this substituent. With this investigation, we identified an irreversible rhodesain inhibitor (i.\u2009e., <jats:bold>2\u2009g<\/jats:bold>) with a <jats:italic>k<\/jats:italic><jats:sub>2nd<\/jats:sub> value of 90\u2009000\u2005M<jats:sup>\u22121<\/jats:sup>\u2009min<jats:sup>\u22121<\/jats:sup> that showed antitrypanosomal activity in the low\u2010micromolar range (EC<jats:sub>50<\/jats:sub>=1.25\u2005\u03bcM), this may be considered a promising lead compound in the drug\u2010discovery process for treating human African trypanosomiasis (HAT).<\/jats:p>","DOI":"10.1002\/cmdc.202000158","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T03:59:00Z","timestamp":1587700740000},"page":"995-1001","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Development of Novel Benzodiazepine\u2010Based Peptidomimetics as Inhibitors of Rhodesain from <i>Trypanosoma brucei rhodesiense<\/i>"],"prefix":"10.1002","volume":"15","author":[{"given":"Carla","family":"Di Chio","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santo","family":"Previti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Amendola","sequence":"additional","affiliation":[{"name":"DiSTABiF University of Campania Luigi Vanvitelli  Via Vivaldi 43 81100 Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Cosconati","sequence":"additional","affiliation":[{"name":"DiSTABiF University of Campania Luigi Vanvitelli  Via Vivaldi 43 81100 Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Schirmeister","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Biomedical Sciences University of Mainz  Staudingerweg 5 55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zappal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-2068","authenticated-orcid":false,"given":"Roberta","family":"Ettari","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,5]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/trypanosomiasis-human-african-(sleeping-sickness)."},{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","volume":"390","author":"B\u00fcscher P.","year":"2017","journal-title":"Lancet"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"e1857","DOI":"10.1371\/journal.pntd.0001857","volume":"6","author":"MacLean L.","year":"2012","journal-title":"PLoS Neglected Trop. 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