YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates
Abstract We recently characterized the potent antiplasmodial activity of the aggregated protein dye YAT2150, whose presumed mode of action is the inhibition of protein aggregation in the malaria parasite. Using single-dose and ramping methods, assays were done to select Plasmodium falciparum parasit...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-85346-y |
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| author | Inés Bouzón-Arnáiz Mukul Rawat Rachael Coyle Lionel Brice Feufack-Donfack Malen Ea Agnes Orban Jean Popovici Lucía Román-Álamo Antonino Nicolò Fallica Bárbara Domínguez-Asenjo Javier Moreno Elsa M. Arce Ana Mallo-Abreu Diego Muñoz-Torrero Marcus C. S. Lee Xavier Fernàndez-Busquets |
| author_facet | Inés Bouzón-Arnáiz Mukul Rawat Rachael Coyle Lionel Brice Feufack-Donfack Malen Ea Agnes Orban Jean Popovici Lucía Román-Álamo Antonino Nicolò Fallica Bárbara Domínguez-Asenjo Javier Moreno Elsa M. Arce Ana Mallo-Abreu Diego Muñoz-Torrero Marcus C. S. Lee Xavier Fernàndez-Busquets |
| author_sort | Inés Bouzón-Arnáiz |
| collection | DOAJ |
| description | Abstract We recently characterized the potent antiplasmodial activity of the aggregated protein dye YAT2150, whose presumed mode of action is the inhibition of protein aggregation in the malaria parasite. Using single-dose and ramping methods, assays were done to select Plasmodium falciparum parasites resistant to YAT2150 concentrations ranging from 3× to 0.25× the in vitro IC50 of the compound (in the two-digit nM range) and performed a cross-resistance assessment in P. falciparum lines harboring mutations that make them resistant to a variety of antimalarial drugs. Resistant parasites did not emerge in vitro after 60 days of incubation, which postulates YAT2150 as an ‘irresistible’ antimalarial. The lyophilized compound is stable for at least one year stored at 25 °C. Tests performed in clinical isolates indicated that YAT2150 had also strong activity against Plasmodium vivax (IC50 between 4 and 36 nM) and Leishmania infantum (1.27 and 1.11 µM), placing it as a unique compound with perspectives of becoming the first drug to be used against both malaria and leishmaniasis. |
| format | Article |
| id | doaj-art-67fa3dcf1419461c9e35fa5a64c6dffe |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-67fa3dcf1419461c9e35fa5a64c6dffe2025-01-26T12:27:03ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85346-yYAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolatesInés Bouzón-Arnáiz0Mukul Rawat1Rachael Coyle2Lionel Brice Feufack-Donfack3Malen Ea4Agnes Orban5Jean Popovici6Lucía Román-Álamo7Antonino Nicolò Fallica8Bárbara Domínguez-Asenjo9Javier Moreno10Elsa M. Arce11Ana Mallo-Abreu12Diego Muñoz-Torrero13Marcus C. S. Lee14Xavier Fernàndez-Busquets15Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-University of Barcelona)Wellcome Sanger InstituteWellcome Sanger InstituteMalaria Research Unit, Institut Pasteur du CambodgeMalaria Research Unit, Institut Pasteur du CambodgeMalaria Research Unit, Institut Pasteur du CambodgeMalaria Research Unit, Institut Pasteur du CambodgeBarcelona Institute for Global Health (ISGlobal, Hospital Clínic-University of Barcelona)Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-University of Barcelona)WHO Collaborating Centre for Leishmaniasis, National Centre for Microbiology Instituto de Salud Carlos IIIWHO Collaborating Centre for Leishmaniasis, National Centre for Microbiology Instituto de Salud Carlos IIILaboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, University of BarcelonaLaboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, University of BarcelonaLaboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, University of BarcelonaWellcome Sanger InstituteBarcelona Institute for Global Health (ISGlobal, Hospital Clínic-University of Barcelona)Abstract We recently characterized the potent antiplasmodial activity of the aggregated protein dye YAT2150, whose presumed mode of action is the inhibition of protein aggregation in the malaria parasite. Using single-dose and ramping methods, assays were done to select Plasmodium falciparum parasites resistant to YAT2150 concentrations ranging from 3× to 0.25× the in vitro IC50 of the compound (in the two-digit nM range) and performed a cross-resistance assessment in P. falciparum lines harboring mutations that make them resistant to a variety of antimalarial drugs. Resistant parasites did not emerge in vitro after 60 days of incubation, which postulates YAT2150 as an ‘irresistible’ antimalarial. The lyophilized compound is stable for at least one year stored at 25 °C. Tests performed in clinical isolates indicated that YAT2150 had also strong activity against Plasmodium vivax (IC50 between 4 and 36 nM) and Leishmania infantum (1.27 and 1.11 µM), placing it as a unique compound with perspectives of becoming the first drug to be used against both malaria and leishmaniasis.https://doi.org/10.1038/s41598-025-85346-y |
| spellingShingle | Inés Bouzón-Arnáiz Mukul Rawat Rachael Coyle Lionel Brice Feufack-Donfack Malen Ea Agnes Orban Jean Popovici Lucía Román-Álamo Antonino Nicolò Fallica Bárbara Domínguez-Asenjo Javier Moreno Elsa M. Arce Ana Mallo-Abreu Diego Muñoz-Torrero Marcus C. S. Lee Xavier Fernàndez-Busquets YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates Scientific Reports |
| title | YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates |
| title_full | YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates |
| title_fullStr | YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates |
| title_full_unstemmed | YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates |
| title_short | YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates |
| title_sort | yat2150 is irresistible in plasmodium falciparum and active against plasmodium vivax and leishmania clinical isolates |
| url | https://doi.org/10.1038/s41598-025-85346-y |
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