Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours
BACKGROUND The neglected illness Chagas disease is treated with limited efficacy and adverse effects by old drugs. Due to the low interest of pharmaceutical industry in targeting economically depressed-patients, repurposing is a tool that should be applied because it can introduce new anti-Chagas en...
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| Language: | English |
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2025
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| Online Access: | https://hdl.handle.net/20.500.12008/53058 |
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| _version_ | 1868890139506245632 |
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| author | Veira, Claudia |
| author2 | Benítez, Diego Pérez Díaz, Leticia Álvarez, Guzmán Cerecetto, Hugo Aguilera, Elena |
| author2_role | author author author author author |
| author_browse | Aguilera, Elena Benítez, Diego Cerecetto, Hugo Pérez Díaz, Leticia Veira, Claudia Álvarez, Guzmán |
| author_facet | Veira, Claudia Benítez, Diego Pérez Díaz, Leticia Álvarez, Guzmán Cerecetto, Hugo Aguilera, Elena |
| author_role | author |
| collection | COLIBRI |
| dc.contributor.none.fl_str_mv | Veira Claudia, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica. Benítez Diego, Instituto Pasteur (Montevideo). Pérez Díaz Leticia, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica. Álvarez Guzmán, Universidad de la República (Uruguay). Centro Universitario Litoral Norte Cerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. Aguilera Elena, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica. |
| dc.creator.none.fl_str_mv | Veira, Claudia Benítez, Diego Pérez Díaz, Leticia Álvarez, Guzmán Cerecetto, Hugo Aguilera, Elena |
| dc.date.none.fl_str_mv | 2025-12-19T16:22:54Z 2025-12-19T16:22:54Z 2025 |
| dc.format.none.fl_str_mv | 11 h. application/pdf |
| dc.identifier.none.fl_str_mv | Veira, C, Benítez, D, Pérez Díaz, L, Álvarez, G, [y otros autores]. "Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours". Memórias do Instituto Oswaldo Cruz. [en línea] 2025, 120: e240183. 11 h. DOI: 10.1590/0074-02760240183. 0074-0276 https://hdl.handle.net/20.500.12008/53058 10.1590/0074-02760240183 |
| dc.language.none.fl_str_mv | en_US eng |
| dc.publisher.none.fl_str_mv | Instituto Oswaldo Cruz |
| dc.relation.none.fl_str_mv | Memórias do Instituto Oswaldo Cruz, 2025, 120: e240183. |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess Licencia Creative Commons Atribución (CC - By 4.0) |
| dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
| dc.subject.none.fl_str_mv | Chagas disease Medicines-repositioning Isobologram Synergism - additivity |
| dc.title.none.fl_str_mv | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | BACKGROUND The neglected illness Chagas disease is treated with limited efficacy and adverse effects by old drugs. Due to the low interest of pharmaceutical industry in targeting economically depressed-patients, repurposing is a tool that should be applied because it can introduce new anti-Chagas entities into the clinic at reduced costs. OBJECTIVES To investigate the repurposing/combination of medicines strategies as anti-Chagas treatment. METHODS Epimastigotes, trypomastigotes and amastigotes of Trypanosoma cruzi were in vitro exposed to 28 Uruguayanapproved medicines not previously tested, 28 FDA-approved medicines previously evaluated, and three reference agents. Parasite inhibition was assessed and for the best drugs, in pairs-isobolographic studies, looking for synergism/additivity/antagonism, were done. Macrophages were used to study selectivity. For some relevant agents, we analysed whether medicines mammals´ action mechanisms are operative in epimastigotes-T. cruzi. FINDINGS From the anti-epimastigotes monotherapy-screening, we found that 18% of them showed better/comparable activities than references. Additionally, for the binary-combinations 8% were additive, 4% were synergic and the rest showed antagonism. Favourably, in macrophages-cytotoxicity four of the binary-combinations were antagonists. Naftazone and pinaverium bromide, not previously tested against T. cruzi, maintained their activity against trypomastigotes and amastigotes. The identified action mechanisms open the door to new strategies designing anti-T. cruzi drugs. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_95eb7a2cb5547936ff35dc0e643a75af |
| identifier_str_mv | Veira, C, Benítez, D, Pérez Díaz, L, Álvarez, G, [y otros autores]. "Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours". Memórias do Instituto Oswaldo Cruz. [en línea] 2025, 120: e240183. 11 h. DOI: 10.1590/0074-02760240183. 0074-0276 10.1590/0074-02760240183 |
| instacron_str | Universidad de la República |
| institution | Universidad de la República |
| instname_str | Universidad de la República |
| language | eng |
| language_invalid_str_mv | en_US |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/53058 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| publisher.none.fl_str_mv | Instituto Oswaldo Cruz |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
| spelling | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behavioursVeira, ClaudiaBenítez, DiegoPérez Díaz, LeticiaÁlvarez, GuzmánCerecetto, HugoAguilera, ElenaChagas diseaseMedicines-repositioningIsobologramSynergism - additivityBACKGROUND The neglected illness Chagas disease is treated with limited efficacy and adverse effects by old drugs. Due to the low interest of pharmaceutical industry in targeting economically depressed-patients, repurposing is a tool that should be applied because it can introduce new anti-Chagas entities into the clinic at reduced costs. OBJECTIVES To investigate the repurposing/combination of medicines strategies as anti-Chagas treatment. METHODS Epimastigotes, trypomastigotes and amastigotes of Trypanosoma cruzi were in vitro exposed to 28 Uruguayanapproved medicines not previously tested, 28 FDA-approved medicines previously evaluated, and three reference agents. Parasite inhibition was assessed and for the best drugs, in pairs-isobolographic studies, looking for synergism/additivity/antagonism, were done. Macrophages were used to study selectivity. For some relevant agents, we analysed whether medicines mammals´ action mechanisms are operative in epimastigotes-T. cruzi. FINDINGS From the anti-epimastigotes monotherapy-screening, we found that 18% of them showed better/comparable activities than references. Additionally, for the binary-combinations 8% were additive, 4% were synergic and the rest showed antagonism. Favourably, in macrophages-cytotoxicity four of the binary-combinations were antagonists. Naftazone and pinaverium bromide, not previously tested against T. cruzi, maintained their activity against trypomastigotes and amastigotes. The identified action mechanisms open the door to new strategies designing anti-T. cruzi drugs.ANII: FCE_3_2022_1_172684Instituto Oswaldo CruzVeira Claudia, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica.Benítez Diego, Instituto Pasteur (Montevideo).Pérez Díaz Leticia, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica.Álvarez Guzmán, Universidad de la República (Uruguay). Centro Universitario Litoral NorteCerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Aguilera Elena, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica.2025-12-19T16:22:54Z2025-12-19T16:22:54Z2025Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 h.application/pdfVeira, C, Benítez, D, Pérez Díaz, L, Álvarez, G, [y otros autores]. "Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours". Memórias do Instituto Oswaldo Cruz. [en línea] 2025, 120: e240183. 11 h. DOI: 10.1590/0074-02760240183.0074-0276https://hdl.handle.net/20.500.12008/5305810.1590/0074-02760240183reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la Repúblicaen_USengMemórias do Instituto Oswaldo Cruz, 2025, 120: e240183.Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/530582026-04-14T10:10:57Z |
| spellingShingle | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours Veira, Claudia Chagas disease Medicines-repositioning Isobologram Synergism - additivity |
| status_str | publishedVersion |
| title | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours |
| title_full | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours |
| title_fullStr | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours |
| title_full_unstemmed | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours |
| title_short | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours |
| title_sort | Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours |
| topic | Chagas disease Medicines-repositioning Isobologram Synergism - additivity |
| url | https://hdl.handle.net/20.500.12008/53058 |