{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:58:20Z","timestamp":1791644300215,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["241615"],"award-info":[{"award-number":["241615"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chagas disease (CD), or American trypanosomiasis, causes more than 10,000 deaths per year in the Americas. Current medical therapy for CD has low efficacy in the chronic phase of the disease and serious adverse effects; therefore, it is necessary to search for new pharmacological treatments. In this work, the ZINC15 database was filtered using the N-acylhydrazone moiety and a subsequent structure-based virtual screening was performed using the cruzain enzyme of Trypanosoma cruzi to predict new potential cruzain inhibitors. After a rational selection process, four compounds, Z2 (ZINC9873043), Z3 (ZINC9870651), Z5 (ZINC9715287), and Z6 (ZINC9861447), were chosen to evaluate their in vitro trypanocidal activity and enzyme inhibition. Compound Z5 showed the best trypanocidal activity against epimatigote (IC50 = 36.26 \u00b1 9.9 \u03bcM) and trypomastigote (IC50 = 166.21 \u00b1 14.5 \u03bcM and 185.1 \u00b1 8.5 \u03bcM on NINOA and INC-5 strains, respectively) forms of Trypanosoma cruzi. In addition, Z5 showed a better inhibitory effect on Trypanosoma cruzi proteases than S1 (STK552090, 8-chloro-N-(3-morpholinopropyl)-5H-pyrimido[5,4-b]-indol-4-amine), a known cruzain inhibitor. This study encourages the use of computational tools for the rational search for trypanocidal drugs.<\/jats:p>","DOI":"10.3390\/ijms20071742","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T05:58:07Z","timestamp":1554789487000},"page":"1742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors"],"prefix":"10.3390","volume":"20","author":[{"given":"Ver\u00f3nica","family":"Herrera-Mayorga","sequence":"first","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"},{"name":"Departamento de Ingenier\u00eda Bioqu\u00edmica, Unidad Acad\u00e9mica Multidisciplinaria Mante, Universidad Aut\u00f3noma de Tamaulipas, Mante 89840, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar E.","family":"Lara-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social (IMSS), Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla F.","family":"Chac\u00f3n-Vargas","sequence":"additional","affiliation":[{"name":"Departamento de Parasitolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1495-0245","authenticated-orcid":false,"given":"Charmina","family":"Aguirre-Alvarado","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11340, Mexico"},{"name":"Unidad de Investigaci\u00f3n en Infectolog\u00eda e Inmunolog\u00eda, Centro M\u00e9dico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de M\u00e9xico 029990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-8378","authenticated-orcid":false,"given":"Lorena","family":"Rodr\u00edguez-P\u00e1ez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5456-3920","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Alc\u00e1ntara-Farf\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1302-6790","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Cordero-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Nogueda-Torres","sequence":"additional","affiliation":[{"name":"Departamento de Parasitolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0727-8251","authenticated-orcid":false,"given":"Francisco","family":"Reyes-Espinosa","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virgilio","family":"Bocanegra-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9842-4167","authenticated-orcid":false,"given":"Gildardo","family":"Rivera","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1128\/CMR.00005-11","article-title":"Trypanosoma cruzi and Chagas\u2019 Disease in the United States","volume":"24","author":"Bern","year":"2011","journal-title":"Clin. 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