Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability

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  • dc.contributor.author Román-Álamo, Lucía
  • dc.contributor.author Avalos-Padilla, Yunuen
  • dc.contributor.author Bouzón-Arnáiz, Inés
  • dc.contributor.author Iglesias, Valentin
  • dc.contributor.author Fernández Lajo, Jorge
  • dc.contributor.author Monteiro, Juan M.
  • dc.contributor.author Rivas, Luis
  • dc.contributor.author Fisa, Roser
  • dc.contributor.author Riera, Cristina
  • dc.contributor.author Andreu Martínez, David
  • dc.contributor.author Pintado-Grima, Carlos
  • dc.contributor.author Ventura, Salvador
  • dc.contributor.author Arce, Elsa M.
  • dc.contributor.author Muñoz-Torrero, Diego
  • dc.contributor.author Fernàndez Busquets, Xavier
  • dc.date.accessioned 2024-04-17T06:22:41Z
  • dc.date.available 2024-04-17T06:22:41Z
  • dc.date.issued 2024
  • dc.description.abstract 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.
  • dc.description.sponsorship This work was supported by grants (i) Fundació La Marató de TV3, Ref. 201811 (X.F.-B.); (ii) PID2021-128325OB-I00 (X.F.-B.) and PID2020-118127RB-I00 (D.M.-T.), funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (MCIN/AEI/10.13039/501100011033), which included ERDF funds; (iii) II Premis Innovació Campus Clínic 2022, Hospital Clínic de Barcelona (X.F.-B.); and (iv) Generalitat de Catalunya, Spain (http://agaur.gencat.cat/), grant numbers 2021-SGR-00635 (S.V.) and 2021-SGR-00357 (D.M.-T.). Work at Pompeu Fabra University was supported by “La Caixa” Banking Foundation (https://fundacionlacaixa.org/, grant HR17-00409) and by grant AGL2017-84097-C2-2-R and the “María de Maeztu” Program for Units of Excellence in R&D from the Spanish Ministry of Science, Innovation and Universities. Work at the Centro de Investigaciones Biológicas was supported by grants from MCIN Subdirección General de Redes y Centros de Investigación Cooperativa-FEDER RD16/0027/0010 and CSIC PIE 201620E038. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Román-Álamo L, Avalos-Padilla Y, Bouzón-Arnáiz I, Iglesias V, Fernández-Lajo J, Monteiro JM, et al. Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability. Antimicrob Agents Chemother. 2024 Mar 6;68(3):e0112723. DOI: 10.1128/aac.01127-23
  • dc.identifier.doi http://dx.doi.org/10.1128/aac.01127-23
  • dc.identifier.issn 0066-4804
  • dc.identifier.uri http://hdl.handle.net/10230/59805
  • dc.language.iso eng
  • dc.publisher American Society for Microbiology
  • dc.relation.ispartof Antimicrob Agents Chemother. 2024 Mar 6;68(3):e0112723
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000806-S
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-128325OB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-118127RB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/AGL2017-84097-C2-2-R
  • dc.rights © 2024 Román-Álamo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Leishmania
  • dc.subject.keyword YAT2150
  • dc.subject.keyword Antileishmanial drugs
  • dc.subject.keyword Protein aggregation
  • dc.title Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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