{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:15:21Z","timestamp":1774876521678,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretaria de Investigacion y Posgrado del Instituto Polit\u00e9cnico Nacional","award":["20250835"],"award-info":[{"award-number":["20250835"]}]},{"name":"Secretaria de Investigacion y Posgrado del Instituto Polit\u00e9cnico Nacional","award":["CBF-2023-2024-2740"],"award-info":[{"award-number":["CBF-2023-2024-2740"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, a drug repurposing strategy was implemented with the aim of identifying new trypanocidal agents against Trypanosoma cruzi (T. cruzi). A total of 924 Food and Drug Administration (FDA)-approved drugs were screened by molecular docking on three sites of trypanothione synthetase (TS), including the catalytic site, a blind docking site, and a potential allosteric site. Selected compounds were further evaluated through in vitro and in vivo assays. Tadalafil, Zafirlukast, Raltegravir, and Olmesartan had better trypanocidal activity than the reference drugs Benznidazole and Nifurtimox in the in vitro evaluation against the trypomastigote form. Additionally, these drugs were able to decrease parasitemia by 20\u201350% in mice in an acute treatment. Molecular dynamics simulations (MDS) at 120 ns helped link findings from in vitro\/in vivo experiments to a potential mechanism of action targeting T. cruzi trypanothione synthetase (TcTS). Therefore, the results encourage the use of these drugs to develop new anti-T. cruzi agents.<\/jats:p>","DOI":"10.3390\/molecules31071139","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:11:59Z","timestamp":1774872719000},"page":"1139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An In Silico and In Vitro Approach Identified Potential Trypanothione Synthetase Inhibitors with Trypanocidal Activity"],"prefix":"10.3390","volume":"31","author":[{"given":"Rogelio","family":"G\u00f3mez-Escobedo","sequence":"first","affiliation":[{"name":"Departamento de Parasitolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domingo","family":"M\u00e9ndez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma D.","family":"Paz-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3800-0228","authenticated-orcid":false,"given":"Eyra","family":"Ortiz-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9327-9658","authenticated-orcid":false,"given":"Lenci K.","family":"V\u00e1zquez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6144-5439","authenticated-orcid":false,"given":"Ana Ver\u00f3nica","family":"Mart\u00ednez-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8915-7351","authenticated-orcid":false,"given":"Timoteo","family":"Delgado-Maldonado","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5729-3344","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Quintero-Solano","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Farmac\u00e9utica, Centro de Biotecnolog\u00eda Gen\u00f3mica, Instituto Polit\u00e9cnico Nacional, Reynosa 88710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Citlali","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8661-9813","authenticated-orcid":false,"given":"Emma","family":"Saavedra","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-607X","authenticated-orcid":false,"given":"Guadalupe","family":"Avalos-Navarro","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas y de la Vida, Centro Universitario de la Ci\u00e9nega (CUCI\u00c9NEGA), Universidad de Guadalajara, Av. 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