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Although the number of people infected is very high, the only drugs available to treat CD, nifurtimox (Nfx) and benznidazole, are highly toxic, particularly in the chronic stage of the disease. Coumarins are a large class of compounds that display a wide range of interesting biological properties, such as antiparasitic. Hence, the aim of this work is to find a good antitrypanosomal drug with less toxicity. The use of simple organism models has become increasingly attractive for planning and simplifying efficient drug discovery. Within these models, <jats:italic>Caenorhabditis elegans<\/jats:italic> has emerged as a convenient and versatile tool with significant advantages for the toxicological potential identification for new compounds.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Trypanocidal activity:<\/jats:p>\n                <jats:p>Forty-two 4-methylamino-coumarins were assayed against the epimastigote form of <jats:italic>Trypanosoma cruzi<\/jats:italic> (Tulahuen 2 strain) by inhibitory concentration 50% (IC<jats:sub>50<\/jats:sub>).<\/jats:p>\n                <jats:p>Toxicity assays:<\/jats:p>\n                <jats:p>Lethal dose 50% (LD<jats:sub>50<\/jats:sub>) and Body Area were determined by <jats:italic>Caenorhabditis elegans<\/jats:italic> N2 strain (wild type) after acute exposure.<\/jats:p>\n                <jats:p>Structure-activity relationship:<\/jats:p>\n                <jats:p>A classificatory model was built using 3D descriptors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Two of these coumarins demonstrated near equipotency to Nifurtimox (IC<jats:sub>50<\/jats:sub>\u2009=\u20095.0\u2009\u00b1\u20091\u2009\u03bcM), with values of: 11\u2009h (LaSOM 266), (IC<jats:sub>50<\/jats:sub>\u2009=\u20096.4\u2009\u00b1\u20091\u2009\u03bcM) and 11\u2009g (LaSOM 231), (IC<jats:sub>50<\/jats:sub>\u2009=\u20098.2\u2009\u00b1\u20092.3\u2009\u03bcM). In <jats:italic>C. elegans<\/jats:italic> it was possible to observe that Nfx showed greater toxicity in both the LD<jats:sub>50<\/jats:sub> assay and the evaluation of the development of worms. It is possible to observe that the efficacy between Nfx and the synthesized compounds (11\u2009h and 11\u2009g) are similar. On the other hand, the toxicity of Nfx is approximately three times higher than that of the compounds. Results from the QSAR-3D study indicate that the volume and hydrophobicity of the substituents have a significant impact on the trypanocidal activities for derivatives that cause more than 50% of inhibition. These results show that the <jats:italic>C. elegans<\/jats:italic> model is efficient for screening potentially toxic compounds.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Two coumarins (11\u2009h and 11\u2009g) showed activity against <jats:italic>T. cruzi<\/jats:italic> epimastigote similar to Nifurtimox, however with lower toxicity in both LD<jats:sub>50<\/jats:sub> and development of <jats:italic>C. elegans<\/jats:italic> assays. These two compounds may be a feasible starting point for the development of new trypanocidal drugs.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40360-019-0357-z","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T01:02:34Z","timestamp":1576717354000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel coumarins active against Trypanosoma cruzi and toxicity assessment using the animal model Caenorhabditis elegans"],"prefix":"10.1186","volume":"20","author":[{"given":"Fabiana Gomes Nascimento","family":"Soares","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"G\u00f6ethel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano Porto","family":"Kagami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Machado","family":"das Neves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Sauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estefania","family":"Birriel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Varela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itamar Lu\u00eds","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilsane","family":"Von Poser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel F\u00e1bio","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1vero Reisdorfer","family":"Paula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo Borges","family":"de Melo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solange Cristina","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Cerecetto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera Lucia","family":"Eifler-Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"357_CR1","volume-title":"Chagas disease (American trypanosomiasis)","author":"Organization WH","year":"2017","unstructured":"Organization WH. 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