{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:01:10Z","timestamp":1789682470489,"version":"4.0.1"},"reference-count":49,"publisher":"Cambridge University Press (CUP)","issue":"11","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In previous studies, we have identified several families of 5-nitroindazole derivatives as promising antichagasic prototypes. Among them, 1-(2-aminoethyl)-2-benzyl-5-nitro-1,2-dihydro-3\n                    <jats:italic>H<\/jats:italic>\n                    -indazol-3-one, (hydrochloride) and 1-(2-acetoxyethyl)-2-benzyl-5-nitro-1,2-dihydro-3\n                    <jats:italic>H<\/jats:italic>\n                    -indazol-3-one (compounds 16 and 24, respectively) have recently shown outstanding activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    over the drug-sensitive\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    CL strain (DTU TcVI). Here, we explored the activity of these derivatives against the moderately drug-resistant Y strain (DTU TcII),\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo.<\/jats:italic>\n                    The outcomes confirmed their activity over replicative forms, showing IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.49 (16) and 5.75\n                    <jats:italic>\u03bc<\/jats:italic>\n                    <jats:sc>m<\/jats:sc>\n                    (24) towards epimastigotes, 0.41 (16) and 1.17\n                    <jats:italic>\u03bc<\/jats:italic>\n                    <jats:sc>m<\/jats:sc>\n                    (24) against intracellular amastigotes. These results, supported by the lack of toxicity on cardiac cells, led to better selectivities than benznidazole (BZ). Otherwise, they were not as active as BZ\n                    <jats:italic>in vitro<\/jats:italic>\n                    against the non-replicative form of the parasite, i.e. bloodstream trypomastigotes.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , acute toxicity assays revealed the absence of toxic events when administered to mice. Moreover, different therapeutic schemes pointed to their capability for decreasing the parasitaemia of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    Y acute infected mice, reaching up to 60% of reduction at the peak day as monotherapy (16), 79.24 and 91.11% when 16 and 24 were co-administered with BZ. These combined therapies had also a positive impact over the mortality, yielding survivals of 83.33 and 66.67%, respectively, while untreated animals reached a cumulative mortality of 100%. These findings confirm the 5-nitroindazole scaffold as a putative prototype for developing novel drugs potentially applicable to the treatment of Chagas disease and introduce their suitability to act in combination with the reference drug.\n                  <\/jats:p>","DOI":"10.1017\/s0031182020000955","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T09:14:32Z","timestamp":1591953272000},"page":"1216-1228","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":8,"title":["Activity profile of two 5-nitroindazole derivatives over the moderately drug-resistant\n                    <i>Trypanosoma cruzi<\/i>\n                    Y strain (DTU TcII):\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    studies"],"prefix":"10.1017","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-900X","authenticated-orcid":false,"given":"Cristina","family":"Fonseca-Berzal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane Fran\u00e7a","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise da Gama Jaen","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Melo","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Cumella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Meuser","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raiza Brand\u00e3o","family":"Peres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Silva da Gama Nefertiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Escario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"G\u00f3mez-Barrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente J.","family":"Ar\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0078-6106","authenticated-orcid":false,"given":"Maria de Nazar\u00e9 Correia","family":"Soeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"S0031182020000955_ref23","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800512"},{"key":"S0031182020000955_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2019.105161"},{"key":"S0031182020000955_ref39","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182019000374"},{"key":"S0031182020000955_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2015.06.013"},{"key":"S0031182020000955_ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.10.009"},{"key":"S0031182020000955_ref22","doi-asserted-by":"publisher","DOI":"10.15420\/ecr.2018.30.2"},{"key":"S0031182020000955_ref12","doi-asserted-by":"publisher","DOI":"10.1017\/pao.2015.4"},{"key":"S0031182020000955_ref34","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16-0761"},{"key":"S0031182020000955_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.09.176"},{"key":"S0031182020000955_ref35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.06.040"},{"key":"S0031182020000955_ref32","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-006-0126-y"},{"key":"S0031182020000955_ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-013-3740-5"},{"key":"S0031182020000955_ref46","unstructured":"World Health Organization (2017) Integrating Neglected Tropical Diseases into Global Health and Development. Fourth WHO report on neglected tropical diseases. 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XXI Congreso de la Sociedad Espa\u00f1ola de Parasitolog\u00eda, Pontevedra, Spain, Abstract book, 296 [97]."},{"key":"S0031182020000955_ref19","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182017001469"},{"key":"S0031182020000955_ref20","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00253"},{"key":"S0031182020000955_ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.12.025"},{"key":"S0031182020000955_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.12.011"},{"key":"S0031182020000955_ref18","unstructured":"Fonseca-Berzal, C , da Silva, CF , Batista, MM , Guedes-da-Silva, FH , Vasconcelos, M , Demarque, KC , Escario, JA , Ar\u00e1n, VJ , G\u00f3mez-Barrio, A and Soeiro, MNC (2019 b) In vivo assessment of the activity of compound 2-benzyl-1-(3-methylaminopropyl)-5-nitro-1,2-dihydro-3H-indazol-3-one (hydrochloride) against Trypanosoma cruzi. 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Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}