دورية أكاديمية
Identification of Inhibitors to trypanosoma cruzi sirtuins based on compounds developed to human enzymes
| العنوان: | Identification of Inhibitors to trypanosoma cruzi sirtuins based on compounds developed to human enzymes |
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| المؤلفون: | Matutino Bastos, Tanira, Botelho Pereira Soares, Milena, Haddad Franco, Caio, Alcântara, Laura, Antonini, Lorenzo, Sabatino, Manuela, Mautone, Nicola, Holanda Freitas-Junior, Lucio, Moraes, Carolina Borsoi, Ragno, Rino, Rotili, Dante, Schenkman, Sergio, Mai, Antonello, Silvio Moretti, Nilmar |
| المساهمون: | Matutino Bastos, Tanira, Botelho Pereira Soares, Milena, Haddad Franco, Caio, Alcântara, Laura, Antonini, Lorenzo, Sabatino, Manuela, Mautone, Nicola, Holanda Freitas-Junior, Lucio, Moraes, Carolina Borsoi, Ragno, Rino, Rotili, Dante, Schenkman, Sergio, Mai, Antonello, Silvio Moretti, Nilmar |
| سنة النشر: | 2020 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| مصطلحات موضوعية: | sirtuin, Trypanosoma cruzi, sirtuin inhibitor, deacetylation |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32455951; info:eu-repo/semantics/altIdentifier/wos/WOS:000539312100255; volume:21; issue:10; numberofpages:16; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11573/1401342Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85085293622 |
| DOI: | 10.3390/ijms21103659 |
| الإتاحة: | https://doi.org/10.3390/ijms21103659Test http://hdl.handle.net/11573/1401342Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6985FC22 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms21103659 |
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