{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:34:07Z","timestamp":1781278447326,"version":"3.54.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI06420"],"award-info":[{"award-number":["AI06420"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"MCTI | Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Therapies for human African trypanosomiasis and Chagas disease, caused by\n            <jats:named-content content-type=\"genus-species\">Trypanosoma brucei<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">Trypanosoma cruzi<\/jats:named-content>\n            , respectively, are limited, providing minimal therapeutic options for the millions of individuals living in very poor communities. Here the effects of 10 novel quinolines are evaluated\n            <jats:italic>in silico<\/jats:italic>\n            and by phenotypic studies using\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            models. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties revealed that most molecules did not infringe on Lipinski's rules, which is a prediction of good oral absorption. These quinolines showed high probabilities of Caco2 permeability and human intestinal absorption and low probabilities of mutagenicity and of hERG1 inhibition.\n            <jats:italic>In vitro<\/jats:italic>\n            screens against bloodstream forms of\n            <jats:named-content content-type=\"genus-species\">T. cruzi<\/jats:named-content>\n            demonstrated that all quinolines were more active than the reference drug (benznidazole [Bz]), except for DB2171 and DB2192, with five (DB2187, DB2131, DB2186, DB2191, and DB2217) displaying 50% effective concentrations (EC\n            <jats:sub>50<\/jats:sub>\n            s) of &lt;3 \u03bcM (4-fold lower than that of Bz). Nine quinolines were more effective than Bz (2.7 \u03bcM) against amastigotes, showing EC\n            <jats:sub>50<\/jats:sub>\n            s ranging from 0.6 to 0.1 \u03bcM. All quinolines were also highly active\n            <jats:italic>in vitro<\/jats:italic>\n            against African trypanosomes, showing EC\n            <jats:sub>50<\/jats:sub>\n            s of \u22640.25 \u03bcM. The most potent and highly selective candidates for each parasite species were tested in\n            <jats:italic>in vivo<\/jats:italic>\n            models. Results for DB2186 were promising in mice with\n            <jats:named-content content-type=\"genus-species\">T. cruzi<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">T. brucei<\/jats:named-content>\n            infections, reaching a 70% reduction of the parasitemia load for\n            <jats:named-content content-type=\"genus-species\">T. cruzi<\/jats:named-content>\n            , and it cured 2 out of 4 mice infected with\n            <jats:named-content content-type=\"genus-species\">T. brucei<\/jats:named-content>\n            . DB2217 was also active\n            <jats:italic>in vivo<\/jats:italic>\n            and cured all 4 mice (100% cure rate) with\n            <jats:named-content content-type=\"genus-species\">T. brucei<\/jats:named-content>\n            infection.\n          <\/jats:p>","DOI":"10.1128\/aac.01936-17","type":"journal-article","created":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T16:44:50Z","timestamp":1512405890000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["<i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            Studies of the Trypanocidal Effect of Novel Quinolines"],"prefix":"10.1128","volume":"62","author":[{"given":"A. S. G.","family":"Nefertiti","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. M.","family":"Batista","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. B.","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. G. J.","family":"Batista","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. F.","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. B.","family":"Peres","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2240-4519","authenticated-orcid":false,"given":"E. C.","family":"Torres-Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanossomat\u00eddeos, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. F.","family":"Cunha-Junior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanossomat\u00eddeos, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Holt","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Georgia State University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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