Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis

Detalhes bibliográficos
Autor(a) principal: Weber, Juliana Inês
Data de Publicação: 2021
Outros Autores: Rigo, Graziela de Vargas, Rocha, Débora Assumpção, Fortes, Isadora Serraglio, Seixas, Adriana, Andrade, Saulo Fernandes de, Tasca, Tiana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/253595
Resumo: Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria.
id UFRGS-2_dfc14c64bd0640907eb70f006ff9b347
oai_identifier_str oai:www.lume.ufrgs.br:10183/253595
network_acronym_str UFRGS-2
network_name_str Repositório Institucional da UFRGS
repository_id_str
spelling Weber, Juliana InêsRigo, Graziela de VargasRocha, Débora AssumpçãoFortes, Isadora SerraglioSeixas, AdrianaAndrade, Saulo Fernandes deTasca, Tiana2023-01-12T04:55:59Z20210753-3322http://hdl.handle.net/10183/253595001156749Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria.application/pdfengBiomedicine & pharmacotherapy. Paris. Vol. 139 (July 2021), 111611, 11 p.Trichomonas vaginalisQuinazolinasMorte celularPeptídeo hidrolasesAmitochondriateQuinazolineCell deathPeptidasesModulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalisEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001156749.pdf.txt001156749.pdf.txtExtracted Texttext/plain60856http://www.lume.ufrgs.br/bitstream/10183/253595/2/001156749.pdf.txt8076175a4ef323c42d5dc34dece397a0MD52ORIGINAL001156749.pdfTexto completo (inglês)application/pdf4330742http://www.lume.ufrgs.br/bitstream/10183/253595/1/001156749.pdf5abc11032ac23588903082befe997e09MD5110183/2535952023-01-13 06:03:25.261508oai:www.lume.ufrgs.br:10183/253595Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-01-13T08:03:25Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
title Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
spellingShingle Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
Weber, Juliana Inês
Trichomonas vaginalis
Quinazolinas
Morte celular
Peptídeo hidrolases
Amitochondriate
Quinazoline
Cell death
Peptidases
title_short Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
title_full Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
title_fullStr Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
title_full_unstemmed Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
title_sort Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis
author Weber, Juliana Inês
author_facet Weber, Juliana Inês
Rigo, Graziela de Vargas
Rocha, Débora Assumpção
Fortes, Isadora Serraglio
Seixas, Adriana
Andrade, Saulo Fernandes de
Tasca, Tiana
author_role author
author2 Rigo, Graziela de Vargas
Rocha, Débora Assumpção
Fortes, Isadora Serraglio
Seixas, Adriana
Andrade, Saulo Fernandes de
Tasca, Tiana
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Weber, Juliana Inês
Rigo, Graziela de Vargas
Rocha, Débora Assumpção
Fortes, Isadora Serraglio
Seixas, Adriana
Andrade, Saulo Fernandes de
Tasca, Tiana
dc.subject.por.fl_str_mv Trichomonas vaginalis
Quinazolinas
Morte celular
Peptídeo hidrolases
topic Trichomonas vaginalis
Quinazolinas
Morte celular
Peptídeo hidrolases
Amitochondriate
Quinazoline
Cell death
Peptidases
dc.subject.eng.fl_str_mv Amitochondriate
Quinazoline
Cell death
Peptidases
description Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2023-01-12T04:55:59Z
dc.type.driver.fl_str_mv Estrangeiro
info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10183/253595
dc.identifier.issn.pt_BR.fl_str_mv 0753-3322
dc.identifier.nrb.pt_BR.fl_str_mv 001156749
identifier_str_mv 0753-3322
001156749
url http://hdl.handle.net/10183/253595
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.pt_BR.fl_str_mv Biomedicine & pharmacotherapy. Paris. Vol. 139 (July 2021), 111611, 11 p.
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFRGS
instname:Universidade Federal do Rio Grande do Sul (UFRGS)
instacron:UFRGS
instname_str Universidade Federal do Rio Grande do Sul (UFRGS)
instacron_str UFRGS
institution UFRGS
reponame_str Repositório Institucional da UFRGS
collection Repositório Institucional da UFRGS
bitstream.url.fl_str_mv http://www.lume.ufrgs.br/bitstream/10183/253595/2/001156749.pdf.txt
http://www.lume.ufrgs.br/bitstream/10183/253595/1/001156749.pdf
bitstream.checksum.fl_str_mv 8076175a4ef323c42d5dc34dece397a0
5abc11032ac23588903082befe997e09
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)
repository.mail.fl_str_mv
_version_ 1801225078640214016

Registros relacionados