{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:31:54Z","timestamp":1787016714946,"version":"build-2736575974"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Schistosoma mansoni<\/jats:named-content>\n                    CB1 (SmCB1), the major cysteine proteases from\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma cruzi<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma brucei<\/jats:named-content>\n                    , and\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. mansoni<\/jats:named-content>\n                    , respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC\n                    <jats:sub>50<\/jats:sub>\n                    s) of \u226410 \u03bcM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 1.2 \u00b1 1.0 \u03bcM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated\n                    <jats:italic>in vitro<\/jats:italic>\n                    against the parasites\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. brucei<\/jats:named-content>\n                    , and\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. mansoni<\/jats:named-content>\n                    , revealing active compounds among this series.\n                  <\/jats:p>","DOI":"10.1128\/aac.04601-14","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T08:04:11Z","timestamp":1424937851000},"page":"2666-2677","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["Synthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity Relationship versus the Parasite Cysteine Proteases Rhodesain, Cruzain, and Schistosoma mansoni Cathepsin B1"],"prefix":"10.1128","volume":"59","author":[{"given":"Nayara Cristina","family":"Fonseca","sequence":"first","affiliation":[{"name":"Departamento de Produtos Farmac\u00eauticos, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Faria","family":"da Cruz","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias 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