{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:24:42Z","timestamp":1778657082928,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T00:00:00Z","timestamp":1590105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/09948-0"],"award-info":[{"award-number":["2018\/09948-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/22031-0"],"award-info":[{"award-number":["2015\/22031-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006181","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","award":["PNX0002\/2014"],"award-info":[{"award-number":["PNX0002\/2014"]}],"id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico Tecnol\u00f3gico (CNPq)","award":["424729\/2018-0"],"award-info":[{"award-number":["424729\/2018-0"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico Tecnol\u00f3gico (CNPq)","award":["477143\/2011-3"],"award-info":[{"award-number":["477143\/2011-3"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico Tecnol\u00f3gico (CNPq)","award":["445655\/2014-3"],"award-info":[{"award-number":["445655\/2014-3"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico Tecnol\u00f3gico (CNPq)","award":["INCT-Vacinas"],"award-info":[{"award-number":["INCT-Vacinas"]}]},{"name":"PRIN 2016","award":["prot. 20152TE5PK"],"award-info":[{"award-number":["prot. 20152TE5PK"]}]},{"name":"AIRC 2016","award":["n. 19162"],"award-info":[{"award-number":["n. 19162"]}]},{"name":"PE-2013-02355271","award":["02355271"],"award-info":[{"award-number":["02355271"]}]},{"name":"PRIN 2017","award":["prot. 2017JL8SRX"],"award-info":[{"award-number":["prot. 2017JL8SRX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi, affecting more than 7 million people in the world. Benznidazole and nifurtimox are the only drugs available for treatment and in addition to causing several side effects, are only satisfactory in the acute phase of the disease. Sirtuins are NAD+-dependent deacetylases involved in several biological processes, which have become drug target candidates in various disease settings. T. cruzi presents two sirtuins, one cytosolic (TcSir2rp1) and the latter mitochondrial (TcSir2rp3). Here, we characterized the effects of human sirtuin inhibitors against T. cruzi sirtuins as an initial approach to develop specific parasite inhibitors. We found that, of 33 compounds tested, two inhibited TcSir2rp1 (15 and 17), while other five inhibited TcSir2rp3 (8, 12, 13, 30, and 32), indicating that specific inhibitors can be devised for each one of the enzymes. Furthermore, all inhibiting compounds prevented parasite proliferation in cultured mammalian cells. When combining the most effective inhibitors with benznidazole at least two compounds, 17 and 32, demonstrated synergistic effects. Altogether, these results support the importance of exploring T. cruzi sirtuins as drug targets and provide key elements to develop specific inhibitors for these enzymes as potential targets for Chagas disease treatment.<\/jats:p>","DOI":"10.3390\/ijms21103659","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T10:18:18Z","timestamp":1590142698000},"page":"3659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-7572","authenticated-orcid":false,"given":"Tanira","family":"Matutino Bastos","sequence":"first","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, FIOCRUZ, Salvador 40296710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Botelho Pereira Soares","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, FIOCRUZ, Salvador 40296710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2467-9401","authenticated-orcid":false,"given":"Caio","family":"Haddad Franco","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade de S\u00e3o Paulo-USP, S\u00e3o Paulo 05508900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-7405","authenticated-orcid":false,"given":"Laura","family":"Alc\u00e2ntara","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade de S\u00e3o Paulo-USP, S\u00e3o Paulo 05508900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Antonini","sequence":"additional","affiliation":[{"name":"Rome Center for Molecular Design, Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9127-3925","authenticated-orcid":false,"given":"Manuela","family":"Sabatino","sequence":"additional","affiliation":[{"name":"Rome Center for Molecular Design, Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Mautone","sequence":"additional","affiliation":[{"name":"Rome Center for Molecular Design, Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucio","family":"Holanda Freitas-Junior","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade de S\u00e3o Paulo-USP, S\u00e3o Paulo 05508900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0689-2770","authenticated-orcid":false,"given":"Carolina Borsoi","family":"Moraes","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade de S\u00e3o Paulo-USP, S\u00e3o Paulo 05508900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5399-975X","authenticated-orcid":false,"given":"Rino","family":"Ragno","sequence":"additional","affiliation":[{"name":"Rome Center for Molecular Design, Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8428-8763","authenticated-orcid":false,"given":"Dante","family":"Rotili","sequence":"additional","affiliation":[{"name":"Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9353-8480","authenticated-orcid":false,"given":"Sergio","family":"Schenkman","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-2382","authenticated-orcid":false,"given":"Antonello","family":"Mai","sequence":"additional","affiliation":[{"name":"Drug Chemistry and Technology Department, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-2497","authenticated-orcid":false,"given":"Nilmar","family":"Silvio Moretti","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bernatchez, J.A., Chen, E., Hull, M.V., McNamara, C.W., McKerrow, J.H., and Siqueira-Neto, J.L. 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