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Thus, inhibitors of cruzipain are considered promising anti-\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            chemotherapeutic agents. Reversible cruzipain inhibitors containing a nitrile \u201cwarhead\u201d were prepared and demonstrated 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) as potent as 1 nM in baculovirus-generated cruzipain enzyme assays. In epimastigote and intracellular amastigote\n            <jats:italic>in vitro<\/jats:italic>\n            assays, the most potent compounds demonstrated antiparasitic behavior in the 5 to 10 \u03bcM IC\n            <jats:sub>50<\/jats:sub>\n            range; however, trypomastigote production from the amastigote form was \u223c90 to 95% inhibited at 2 \u03bcM. Two key compounds, Cz007 and Cz008, with IC\n            <jats:sub>50<\/jats:sub>\n            s of 1.1 and 1.8 nM, respectively, against the recombinant enzyme were tested in a murine model of acute\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            infection, with oral dosing in chow for 28 days at doses from 3 to 50 mg\/kg of body weight. At 3 mg\/kg of Cz007 and 3 mg\/kg of Cz008, the blood parasitemia areas under the concentration-time curves were 16% and 25% of the untreated group, respectively. At sacrifice, 24 days after immunosuppression with cyclophosphamide, parasite presence in blood, heart, and esophagus was evaluated. Based on negative quantitative PCR results in all three tissues, cure rates in surviving animals were 90% for Cz007 at 3 mg\/kg, 78% for Cz008 at 3 mg\/kg, and 71% for benznidazole, the control compound, at 50 mg\/kg.\n          <\/jats:p>","DOI":"10.1128\/aac.01855-13","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T02:55:08Z","timestamp":1386644108000},"page":"1167-1178","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":87,"title":["Reversible Cysteine Protease Inhibitors Show Promise for a Chagas Disease Cure"],"prefix":"10.1128","volume":"58","author":[{"given":"Momar","family":"Ndao","sequence":"first","affiliation":[{"name":"National Reference Centre for Parasitology, Research Institute of McGill University Health Center, Montreal, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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