Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability

The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a pot...

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Autores: Monteiro, Juan M., Román-Álamo, Lucía, Avalos Padilla, Yunuen, Bouzón Arnáiz, Xavier, Iglesias, Valentín, Fernández-Lajo, Jorge, Rivas, Luis A., Fisa Saladrigas, Roser, Riera Lizandra, Ma. Cristina, Andreu, David, Pintado Grima, Carlos, Ventura, Salvador, Arce, Elsa M., Muñoz-Torrero López-Ibarra, Diego, Fernàndez Busquets, Xavier
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/216109
Acesso em linha:https://hdl.handle.net/2445/216109
Access Level:acceso abierto
Palavra-chave:Leishmaniosi
Parasitologia mèdica
Leishmània
Leishmaniasis
Medical parasitology
Leishmania
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spelling Effect of the aggregated protein dye YAT2150 on Leishmania parasite viabilityMonteiro, Juan M.Román-Álamo, LucíaAvalos Padilla, YunuenBouzón Arnáiz, XavierIglesias, ValentínFernández-Lajo, JorgeRivas, Luis A.Fisa Saladrigas, RoserRiera Lizandra, Ma. CristinaAndreu, DavidPintado Grima, CarlosVentura, SalvadorArce, Elsa M.Muñoz-Torrero López-Ibarra, DiegoFernàndez Busquets, XavierLeishmaniosiParasitologia mèdicaLeishmàniaLeishmaniasisMedical parasitologyLeishmaniaThe problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC50) of approximately 0.5 µM against promastigote and amastigote stages of Leishmania infantum. The encapsulation in liposomes of YAT2150 significantly improved its in vitro IC50 to 0.37 and 0.19 µM in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 µM. YAT2150 became strongly fluorescent when binding intracellular protein deposits in Leishmania cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite Plasmodium falciparum, the inhibition of protein aggregation. In Leishmania major, YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both Plasmodium and Leishmania, thus being a potential drug for the treatment of co-infections of both parasites.American Society for Microbiology2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/216109Articles publicats en revistes (Biologia, Sanitat i Medi Ambient)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1128/aac.01127-23Antimicrobial Agents and Chemotherapy, 2024, vol. 68, num.3, p. e0112723https://doi.org/10.1128/aac.01127-23cc by (c) Juan M. Monteiro, et al., 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2161092026-05-27T06:46:51Z
dc.title.none.fl_str_mv Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
title Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
spellingShingle Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
Monteiro, Juan M.
Leishmaniosi
Parasitologia mèdica
Leishmània
Leishmaniasis
Medical parasitology
Leishmania
title_short Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
title_full Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
title_fullStr Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
title_full_unstemmed Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
title_sort Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
dc.creator.none.fl_str_mv Monteiro, Juan M.
Román-Álamo, Lucía
Avalos Padilla, Yunuen
Bouzón Arnáiz, Xavier
Iglesias, Valentín
Fernández-Lajo, Jorge
Rivas, Luis A.
Fisa Saladrigas, Roser
Riera Lizandra, Ma. Cristina
Andreu, David
Pintado Grima, Carlos
Ventura, Salvador
Arce, Elsa M.
Muñoz-Torrero López-Ibarra, Diego
Fernàndez Busquets, Xavier
author Monteiro, Juan M.
author_facet Monteiro, Juan M.
Román-Álamo, Lucía
Avalos Padilla, Yunuen
Bouzón Arnáiz, Xavier
Iglesias, Valentín
Fernández-Lajo, Jorge
Rivas, Luis A.
Fisa Saladrigas, Roser
Riera Lizandra, Ma. Cristina
Andreu, David
Pintado Grima, Carlos
Ventura, Salvador
Arce, Elsa M.
Muñoz-Torrero López-Ibarra, Diego
Fernàndez Busquets, Xavier
author_role author
author2 Román-Álamo, Lucía
Avalos Padilla, Yunuen
Bouzón Arnáiz, Xavier
Iglesias, Valentín
Fernández-Lajo, Jorge
Rivas, Luis A.
Fisa Saladrigas, Roser
Riera Lizandra, Ma. Cristina
Andreu, David
Pintado Grima, Carlos
Ventura, Salvador
Arce, Elsa M.
Muñoz-Torrero López-Ibarra, Diego
Fernàndez Busquets, Xavier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Leishmaniosi
Parasitologia mèdica
Leishmània
Leishmaniasis
Medical parasitology
Leishmania
topic Leishmaniosi
Parasitologia mèdica
Leishmània
Leishmaniasis
Medical parasitology
Leishmania
description The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC50) of approximately 0.5 µM against promastigote and amastigote stages of Leishmania infantum. The encapsulation in liposomes of YAT2150 significantly improved its in vitro IC50 to 0.37 and 0.19 µM in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 µM. YAT2150 became strongly fluorescent when binding intracellular protein deposits in Leishmania cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite Plasmodium falciparum, the inhibition of protein aggregation. In Leishmania major, YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both Plasmodium and Leishmania, thus being a potential drug for the treatment of co-infections of both parasites.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/216109
url https://hdl.handle.net/2445/216109
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1128/aac.01127-23
Antimicrobial Agents and Chemotherapy, 2024, vol. 68, num.3, p. e0112723
https://doi.org/10.1128/aac.01127-23
dc.rights.none.fl_str_mv cc by (c) Juan M. Monteiro, et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Juan M. Monteiro, et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia, Sanitat i Medi Ambient)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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