1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites

Detalhes bibliográficos
Autor(a) principal: Mendes, Andreia
Data de Publicação: 2022
Outros Autores: Armada, Ana, Cabral, Lília I.L., Amado, Patrícia S.M., Campino, Lenea, Cristiano, Maria L.S., Cortes, Sofia
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/138573
Resumo: Funding Information: This research was funded by Funda??o para a Ci?ncia e Tecnologia (FCT), through projects: IF/00743/2015/CP1320, UID/MULTI/04413/2020(GHTM), UID/MULTI/04326/2021 (CCMAR), and UI0313B/QUI/2020 (CQC), as well as the doctoral grant SFRH/BD/130407/2017 (P.S.M.A.). Funding Information: Funding: This research was funded by Fundação para a Ciência e Tecnologia (FCT), through projects: IF/00743/2015/CP1320, UID/MULTI/04413/2020(GHTM), UID/MULTI/04326/2021 (CCMAR), and UI0313B/QUI/2020 (CQC), as well as the doctoral grant SFRH/BD/130407/2017 (P.S.M.A.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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spelling 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania ParasitesIn Vitro Activity and Mode of Action1,2,4,5-tetraoxanes1,2,4-trioxolanesLeishmania donovaniLeishmania infantumleishmaniasismode of actionreactive oxygen speciesselectivityMolecular MedicinePharmaceutical ScienceDrug DiscoverySDG 3 - Good Health and Well-beingFunding Information: This research was funded by Funda??o para a Ci?ncia e Tecnologia (FCT), through projects: IF/00743/2015/CP1320, UID/MULTI/04413/2020(GHTM), UID/MULTI/04326/2021 (CCMAR), and UI0313B/QUI/2020 (CQC), as well as the doctoral grant SFRH/BD/130407/2017 (P.S.M.A.). Funding Information: Funding: This research was funded by Fundação para a Ciência e Tecnologia (FCT), through projects: IF/00743/2015/CP1320, UID/MULTI/04413/2020(GHTM), UID/MULTI/04326/2021 (CCMAR), and UI0313B/QUI/2020 (CQC), as well as the doctoral grant SFRH/BD/130407/2017 (P.S.M.A.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Leishmaniasis remains one of the ten Neglected Tropical Diseases with significant morbid-ity and mortality in humans. Current treatment of visceral leishmaniasis is difficult due to a lack of effective, non-toxic, and non-extensive medications. This study aimed to evaluate the selectivity of 12 synthetic endoperoxides (1,2,4-trioxolanes; 1,2,4,5-tetraoxanes) and uncover their biochemical effects on Leishmania parasites responsible for visceral leishmaniasis. The compounds were screened for in vitro activity against L. infantum and L. donovani and for cytotoxicity in two monocytic cell lines (J774A.1 and THP-1) using the methyl thiazol tetrazolium assay. Reactive oxygen species formation, apoptosis, and mitochondrial impairment were measured by flow cytometry. The compounds exhib-ited fair to moderate anti-proliferative activity against promastigotes of the 2 Leishmania species, with IC50 values ranging from 13.0 ± 1.7 µM to 793.0 ± 37.2 µM. Tetraoxanes LC132 and LC138 demonstrated good leishmanicidal activity on L. infantum amastigotes (IC50 13.2 ± 5.2 and 23.9 ± 2.7 µM) with low cytotoxicity in mammalian cells (SIs 22.1 and 118.6), indicating selectivity towards the parasite. Furthermore, LC138 was able to induce late apoptosis and dose-dependent oxidative stress without affecting mithocondria. Compounds LC132 and LC138 can be further explored as potential antileishmanial chemotypes.Instituto de Higiene e Medicina Tropical (IHMT)Global Health and Tropical Medicine (GHTM)RUNMendes, AndreiaArmada, AnaCabral, Lília I.L.Amado, Patrícia S.M.Campino, LeneaCristiano, Maria L.S.Cortes, Sofia2022-05-24T22:19:05Z2022-042022-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/138573eng1424-8247PURE: 43621544https://doi.org/10.3390/ph15040446info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:15:48Zoai:run.unl.pt:10362/138573Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:49:07.528622Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
In Vitro Activity and Mode of Action
title 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
spellingShingle 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
Mendes, Andreia
1,2,4,5-tetraoxanes
1,2,4-trioxolanes
Leishmania donovani
Leishmania infantum
leishmaniasis
mode of action
reactive oxygen species
selectivity
Molecular Medicine
Pharmaceutical Science
Drug Discovery
SDG 3 - Good Health and Well-being
title_short 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
title_full 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
title_fullStr 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
title_full_unstemmed 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
title_sort 1,2,4-Trioxolane and 1,2,4,5-Tetraoxane Endoperoxides against Old-World Leishmania Parasites
author Mendes, Andreia
author_facet Mendes, Andreia
Armada, Ana
Cabral, Lília I.L.
Amado, Patrícia S.M.
Campino, Lenea
Cristiano, Maria L.S.
Cortes, Sofia
author_role author
author2 Armada, Ana
Cabral, Lília I.L.
Amado, Patrícia S.M.
Campino, Lenea
Cristiano, Maria L.S.
Cortes, Sofia
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Higiene e Medicina Tropical (IHMT)
Global Health and Tropical Medicine (GHTM)
RUN
dc.contributor.author.fl_str_mv Mendes, Andreia
Armada, Ana
Cabral, Lília I.L.
Amado, Patrícia S.M.
Campino, Lenea
Cristiano, Maria L.S.
Cortes, Sofia
dc.subject.por.fl_str_mv 1,2,4,5-tetraoxanes
1,2,4-trioxolanes
Leishmania donovani
Leishmania infantum
leishmaniasis
mode of action
reactive oxygen species
selectivity
Molecular Medicine
Pharmaceutical Science
Drug Discovery
SDG 3 - Good Health and Well-being
topic 1,2,4,5-tetraoxanes
1,2,4-trioxolanes
Leishmania donovani
Leishmania infantum
leishmaniasis
mode of action
reactive oxygen species
selectivity
Molecular Medicine
Pharmaceutical Science
Drug Discovery
SDG 3 - Good Health and Well-being
description Funding Information: This research was funded by Funda??o para a Ci?ncia e Tecnologia (FCT), through projects: IF/00743/2015/CP1320, UID/MULTI/04413/2020(GHTM), UID/MULTI/04326/2021 (CCMAR), and UI0313B/QUI/2020 (CQC), as well as the doctoral grant SFRH/BD/130407/2017 (P.S.M.A.). Funding Information: Funding: This research was funded by Fundação para a Ciência e Tecnologia (FCT), through projects: IF/00743/2015/CP1320, UID/MULTI/04413/2020(GHTM), UID/MULTI/04326/2021 (CCMAR), and UI0313B/QUI/2020 (CQC), as well as the doctoral grant SFRH/BD/130407/2017 (P.S.M.A.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
publishDate 2022
dc.date.none.fl_str_mv 2022-05-24T22:19:05Z
2022-04
2022-04-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/138573
url http://hdl.handle.net/10362/138573
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1424-8247
PURE: 43621544
https://doi.org/10.3390/ph15040446
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 Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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