Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy
Background/Objectives : YAT2150 is a first-in-class antiplasmodial compound that has been recently proposed as a new interesting drug for malaria therapy. Methods/Results : The fluorescence of YAT2150 rapidly increases upon its entry into Plasmodium, a property that can be of use for the design of h...
| Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | article |
| Publication Date: | 2024 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:307581 |
| Online Access: | https://ddd.uab.cat/record/307581 https://dx.doi.org/urn:doi:10.3390/pharmaceutics16101290 |
| Access Level: | Open access |
| Keyword: | Plasmodium falciparum Malaria Protein aggregation YAT2150 |
| id |
ES_7cf58fcb720b238e0bd55a06eb8e7d27 |
|---|---|
| oai_identifier_str |
oai:ddd.uab.cat:307581 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| dc.title.none.fl_str_mv |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy |
| title |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy |
| spellingShingle |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy Camarero-Hoyos, Claudia Plasmodium falciparum Malaria Protein aggregation YAT2150 |
| title_short |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy |
| title_full |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy |
| title_fullStr |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy |
| title_full_unstemmed |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy |
| title_sort |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy |
| dc.creator.none.fl_str_mv |
Camarero-Hoyos, Claudia Bouzón-Arnáiz, Inés Avalos-Padilla, Yunuen|||0000-0003-4074-5624 Fallica, Antonino Nicolò|||0000-0003-1899-8414 Román-Álamo, Lucía Ramírez Moreno, Miriam|||0000-0002-9823-319X Portabella, Emma Cuspinera, Ona Currea-Ayala, Daniela Orozco-Quer, Marc Ribera, Maria Siden-Kiamos, Inga|||0000-0003-1572-5840 Spanos, Lefteris Iglesias, Valentin|||0000-0002-6133-0869 Crespo, Benigno Viera, Sara|||0000-0002-2025-4804 Andreu Martínez, David|||0000-0002-6317-6666 Sulleiro, Elena|||0000-0002-9783-6060 Zarzuela, Francesc Urtasun, Nerea|||0000-0003-1093-2269 Pérez-Torras, Sandra|||0000-0002-2785-5602 Pastor-Anglada, Marçal|||0000-0003-3712-1773 Arce, Elsa M.|||0000-0003-3757-5468 Muñoz-Torrero López-Ibarra, Diego|||0000-0002-8140-8555 Fernández Busquets, Xavier|||0000-0002-4622-9631 |
| author |
Camarero-Hoyos, Claudia |
| author_facet |
Camarero-Hoyos, Claudia Bouzón-Arnáiz, Inés Avalos-Padilla, Yunuen|||0000-0003-4074-5624 Fallica, Antonino Nicolò|||0000-0003-1899-8414 Román-Álamo, Lucía Ramírez Moreno, Miriam|||0000-0002-9823-319X Portabella, Emma Cuspinera, Ona Currea-Ayala, Daniela Orozco-Quer, Marc Ribera, Maria Siden-Kiamos, Inga|||0000-0003-1572-5840 Spanos, Lefteris Iglesias, Valentin|||0000-0002-6133-0869 Crespo, Benigno Viera, Sara|||0000-0002-2025-4804 Andreu Martínez, David|||0000-0002-6317-6666 Sulleiro, Elena|||0000-0002-9783-6060 Zarzuela, Francesc Urtasun, Nerea|||0000-0003-1093-2269 Pérez-Torras, Sandra|||0000-0002-2785-5602 Pastor-Anglada, Marçal|||0000-0003-3712-1773 Arce, Elsa M.|||0000-0003-3757-5468 Muñoz-Torrero López-Ibarra, Diego|||0000-0002-8140-8555 Fernández Busquets, Xavier|||0000-0002-4622-9631 |
| author_role |
author |
| author2 |
Bouzón-Arnáiz, Inés Avalos-Padilla, Yunuen|||0000-0003-4074-5624 Fallica, Antonino Nicolò|||0000-0003-1899-8414 Román-Álamo, Lucía Ramírez Moreno, Miriam|||0000-0002-9823-319X Portabella, Emma Cuspinera, Ona Currea-Ayala, Daniela Orozco-Quer, Marc Ribera, Maria Siden-Kiamos, Inga|||0000-0003-1572-5840 Spanos, Lefteris Iglesias, Valentin|||0000-0002-6133-0869 Crespo, Benigno Viera, Sara|||0000-0002-2025-4804 Andreu Martínez, David|||0000-0002-6317-6666 Sulleiro, Elena|||0000-0002-9783-6060 Zarzuela, Francesc Urtasun, Nerea|||0000-0003-1093-2269 Pérez-Torras, Sandra|||0000-0002-2785-5602 Pastor-Anglada, Marçal|||0000-0003-3712-1773 Arce, Elsa M.|||0000-0003-3757-5468 Muñoz-Torrero López-Ibarra, Diego|||0000-0002-8140-8555 Fernández Busquets, Xavier|||0000-0002-4622-9631 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Plasmodium falciparum Malaria Protein aggregation YAT2150 |
| topic |
Plasmodium falciparum Malaria Protein aggregation YAT2150 |
| description |
Background/Objectives : YAT2150 is a first-in-class antiplasmodial compound that has been recently proposed as a new interesting drug for malaria therapy. Methods/Results : The fluorescence of YAT2150 rapidly increases upon its entry into Plasmodium, a property that can be of use for the design of highly sensitive diagnostic approaches. YAT2150 blocks the in vitro development of the ookinete stage of Plasmodium and, when added to an infected blood meal, inhibits oocyst formation in the mosquito. Thus, the compound could possibly contribute to future transmission-blocking antimalarial strategies. Cell influx/efflux studies in Caco-2 cells suggest that YAT2150 is internalized by endocytosis and also through the OATP2B1 transporter, whereas its main export route would be via OSTα. YAT2150 has an overall favorable drug metabolism and pharmacokinetics profile, and its moderate cytotoxicity can be significantly reduced upon encapsulation in immunoliposomes, which leads to a dramatic increase in the drug selectivity index to values close to 1000. Although YAT2150 binds amyloid-forming peptides, its in vitro fluorescence emission is stronger upon association with peptides that form amorphous aggregates, suggesting that regions enriched in unstructured proteins are the preferential binding sites of the drug inside Plasmodium cells. The reduction of protein aggregation in the parasite after YAT2150 treatment, which has been suggested to be directly related to the drug's mode of action, is also observed following treatment with quinoline antimalarials like chloroquine and primaquine. Conclusions : Altogether, the data presented here indicate that YAT2150 can represent the spearhead of a new family of compounds for malaria diagnosis and therapy due to its presumed novel mode of action based on the interaction with functional protein aggregates in the pathogen. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2 2024-01-01 2024 2024-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/307581 https://dx.doi.org/urn:doi:10.3390/pharmaceutics16101290 |
| url |
https://ddd.uab.cat/record/307581 https://dx.doi.org/urn:doi:10.3390/pharmaceutics16101290 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-128325OB-I00 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133085-I00 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-118127RB-I00 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 AGL2017-84097-C2-2-R Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-124765OB-I00 Generalitat de Catalunya https://doi.org/10.13039/501100002809 2021SGR00635 Generalitat de Catalunya https://doi.org/10.13039/501100002809 2021SGR00357 "la Caixa" Foundation https://doi.org/10.13039/100010434 HR1700409 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.source.none.fl_str_mv |
reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
| instname_str |
Universitat Autònoma de Barcelona |
| reponame_str |
Dipòsit Digital de Documents de la UAB |
| collection |
Dipòsit Digital de Documents de la UAB |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869411628320030720 |
| spelling |
Leveraging the Aggregated Protein Dye YAT2150 for Malaria ChemotherapyCamarero-Hoyos, ClaudiaBouzón-Arnáiz, InésAvalos-Padilla, Yunuen|||0000-0003-4074-5624Fallica, Antonino Nicolò|||0000-0003-1899-8414Román-Álamo, LucíaRamírez Moreno, Miriam|||0000-0002-9823-319XPortabella, EmmaCuspinera, OnaCurrea-Ayala, DanielaOrozco-Quer, MarcRibera, MariaSiden-Kiamos, Inga|||0000-0003-1572-5840Spanos, LefterisIglesias, Valentin|||0000-0002-6133-0869Crespo, BenignoViera, Sara|||0000-0002-2025-4804Andreu Martínez, David|||0000-0002-6317-6666Sulleiro, Elena|||0000-0002-9783-6060Zarzuela, FrancescUrtasun, Nerea|||0000-0003-1093-2269Pérez-Torras, Sandra|||0000-0002-2785-5602Pastor-Anglada, Marçal|||0000-0003-3712-1773Arce, Elsa M.|||0000-0003-3757-5468Muñoz-Torrero López-Ibarra, Diego|||0000-0002-8140-8555Fernández Busquets, Xavier|||0000-0002-4622-9631Plasmodium falciparumMalariaProtein aggregationYAT2150Background/Objectives : YAT2150 is a first-in-class antiplasmodial compound that has been recently proposed as a new interesting drug for malaria therapy. Methods/Results : The fluorescence of YAT2150 rapidly increases upon its entry into Plasmodium, a property that can be of use for the design of highly sensitive diagnostic approaches. YAT2150 blocks the in vitro development of the ookinete stage of Plasmodium and, when added to an infected blood meal, inhibits oocyst formation in the mosquito. Thus, the compound could possibly contribute to future transmission-blocking antimalarial strategies. Cell influx/efflux studies in Caco-2 cells suggest that YAT2150 is internalized by endocytosis and also through the OATP2B1 transporter, whereas its main export route would be via OSTα. YAT2150 has an overall favorable drug metabolism and pharmacokinetics profile, and its moderate cytotoxicity can be significantly reduced upon encapsulation in immunoliposomes, which leads to a dramatic increase in the drug selectivity index to values close to 1000. Although YAT2150 binds amyloid-forming peptides, its in vitro fluorescence emission is stronger upon association with peptides that form amorphous aggregates, suggesting that regions enriched in unstructured proteins are the preferential binding sites of the drug inside Plasmodium cells. The reduction of protein aggregation in the parasite after YAT2150 treatment, which has been suggested to be directly related to the drug's mode of action, is also observed following treatment with quinoline antimalarials like chloroquine and primaquine. Conclusions : Altogether, the data presented here indicate that YAT2150 can represent the spearhead of a new family of compounds for malaria diagnosis and therapy due to its presumed novel mode of action based on the interaction with functional protein aggregates in the pathogen. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/307581https://dx.doi.org/urn:doi:10.3390/pharmaceutics16101290reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-128325OB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133085-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-118127RB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 AGL2017-84097-C2-2-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-124765OB-I00Generalitat de Catalunya https://doi.org/10.13039/501100002809 2021SGR00635Generalitat de Catalunya https://doi.org/10.13039/501100002809 2021SGR00357"la Caixa" Foundation https://doi.org/10.13039/100010434 HR1700409open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3075812026-06-06T12:50:31Z |
| score |
15,812429 |