| Autor | Bastos, Tanira Matutino | |
| Autor | Soares, Milena Botelho Pereira | |
| Autor | Franco, Caio Haddad | |
| Autor | Alcântara, Laura | |
| Autor | Antonini, Lorenzo | |
| Autor | Sabatino, Manuela | |
| Autor | Mautone, Nicola | |
| Autor | Freitas Junior, Lucio Holanda | |
| Autor | Moraes, Carolina Borsoi | |
| Autor | Ragno, Rino | |
| Autor | Rotili, Dante | |
| Autor | Schenkman, Sergio | |
| Autor | Mai, Antonello | |
| Autor | Moretti, Nilmar Silvio | |
| Data de acesso | 2020-09-23T12:28:30Z | |
| Data de disponibilização | 2020-09-23T12:28:30Z | |
| Data do publicação | 2020 | |
| Citação | BASTOS, Tanira Matutino et al. Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes. International Journal of Molecular Sciences, 2020. | pt_BR |
| ISSN | 1661-6596 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/43563 | |
| Fomento | Fundação de Amparo à Pesquisa do Estado de São Paulo [grant number
2018/09948-0 to NSM and 2015/22031-0 to SS]; Fundação de Amparo à Pesquisa do Estado da Bahia [grant number
PNX0002/2014]; and Conselho Nacional de Desenvolvimento Científico Tecnológico [grant number 424729/2018-0
to NSM and 477143/2011-3, 445655/2014-3, and INCTV, to SS], PRIN 2016 (prot. 20152TE5PK) (to AM), AIRC 2016
(n. 19162) (to AM), and PE-2013-02355271 (to AM), PRIN 2017 (prot. 2017JL8SRX) (to RR). | pt_BR |
| Idioma | eng | pt_BR |
| Editor | MDPI | pt_BR |
| Direito Autoral | open access | pt_BR |
| Palavras-chave | Trypanosoma cruzi | pt_BR |
| Palavras-chave | Inibidores | pt_BR |
| Palavras-chave | Desacetilação | pt_BR |
| Título | Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes | pt_BR |
| Tipo do documento | Article | pt_BR |
| Resumo em Inglês | Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi, a ecting
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 e ects, 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 e ects
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 e ective inhibitors with benznidazole at least
two compounds, 17 and 32, demonstrated synergistic e ects. 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 | pt_BR |
| Afiliação | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Afiliação | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Afiliação | Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil. | pt_BR |
| Afiliação | Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil. | pt_BR |
| Afiliação | Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy. | pt_BR |
| Afiliação | Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy. | pt_BR |
| Afiliação | Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy. | pt_BR |
| Afiliação | Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil. | pt_BR |
| Afiliação | Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil. | pt_BR |
| Afiliação | Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy. | pt_BR |
| Afiliação | Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy. | pt_BR |
| Afiliação | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Afiliação | Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Pasteur Institute, Cenci-Bolognetti Foundation. Rome, Italy. | pt_BR |
| Afiliação | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Palavras-chave em inglês | Trypanosoma cruzi | pt_BR |
| Palavras-chave em inglês | Sirtuin inhibitors | pt_BR |
| Palavras-chave em inglês | Deacetylation | pt_BR |
