Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.

Novel lipophilic hydroxytyrosol N-alkylcarbamate conjugates were synthesized by coupling several alkyl isocyanates of different chain lengths with the primary hydroxy group of this natural phenol. These N-alkylcarbamate conjugates were tested as antitrypanosomal and antileishmanial agents, and their...

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Detalhes bibliográficos
Autores: Jimenez-Martin, Belinda, Guerra-Arias, Diego, Martínez, Antonio, García-Hernández, Raquel, Medina-O'Donnell, Marta, Pérez-Victoria, José M., Rivas, Francisco
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/389758
Acesso em linha:http://hdl.handle.net/10261/389758
Access Level:acceso abierto
Palavra-chave:Hydroxytyrosol
Carbamate group
Antitrypanosomal
Antileishmanial
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spelling Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.Jimenez-Martin, BelindaGuerra-Arias, DiegoMartínez, AntonioGarcía-Hernández, RaquelMedina-O'Donnell, MartaPérez-Victoria, José M.Rivas, FranciscoHydroxytyrosolCarbamate groupAntitrypanosomalAntileishmanialNovel lipophilic hydroxytyrosol N-alkylcarbamate conjugates were synthesized by coupling several alkyl isocyanates of different chain lengths with the primary hydroxy group of this natural phenol. These N-alkylcarbamate conjugates were tested as antitrypanosomal and antileishmanial agents, and their cytotoxicity was evaluated against the human MRC-5 and THP-1 cell lines. Five of these N-alkylcarbamate derivatives showed submicromolar IC concentrations against Trypanosoma brucei brucei, with values ranging from 0.2 to 0.8 μM, and three other hydroxytyrosol conjugates showed IC values below 5 μM. Data for the five most active N-alkylcarbamate derivatives indicate a gain in activity relative to hydroxytyrosol of between 115- and 460-fold, and selectivity indices for control/human MRC-5 cells relative to T. b. brucei parasites of between 47- and 140-fold. These N-alkylcarbamate derivatives were also tested against the intracellular amastigote form of Leishmania donovani in infected THP-1 macrophages, where five compounds had IC values less than or equal to 10 μM, with selectivity indices relative to L. donovani of between 3- and 25-fold in MRC-5 cells and between 8- and 60-fold in THP-1 cells. In all of these derivatives, the ortho-diphenolic groups were free. When the hydroxytyrosol derivatives had ortho-diphenolic groups protected by benzyl groups, cytotoxicity against T. b. brucei and L. donovani showed significantly higher IC values, with most cases exceeding 20 μM.This research was funded by grants from the Junta de Andalucia Consejeria de Economia Innovacion y Ciencia grant number B-FQM-650-UGR20 to FR, the National Plan for Scientific and Technical Research and Innovation 10.13039/501100011033 grant number PID2022-138474OB-I00 to JMPV, and FEDER funds from the EU to JMPV. We thank David Nesbitt for reviewing the English of the manuscript.Peer reviewedAcademic PressJunta de AndalucíaAgencia Estatal de Investigación (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/389758reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.bioorg.2025.108354Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3897582026-05-22T06:33:51Z
dc.title.none.fl_str_mv Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
title Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
spellingShingle Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
Jimenez-Martin, Belinda
Hydroxytyrosol
Carbamate group
Antitrypanosomal
Antileishmanial
title_short Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
title_full Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
title_fullStr Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
title_full_unstemmed Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
title_sort Hydroxytyrosol N-alkylcarbamate conjugates as antitrypanosomal and antileishmanial agents.
dc.creator.none.fl_str_mv Jimenez-Martin, Belinda
Guerra-Arias, Diego
Martínez, Antonio
García-Hernández, Raquel
Medina-O'Donnell, Marta
Pérez-Victoria, José M.
Rivas, Francisco
author Jimenez-Martin, Belinda
author_facet Jimenez-Martin, Belinda
Guerra-Arias, Diego
Martínez, Antonio
García-Hernández, Raquel
Medina-O'Donnell, Marta
Pérez-Victoria, José M.
Rivas, Francisco
author_role author
author2 Guerra-Arias, Diego
Martínez, Antonio
García-Hernández, Raquel
Medina-O'Donnell, Marta
Pérez-Victoria, José M.
Rivas, Francisco
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Junta de Andalucía
Agencia Estatal de Investigación (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Hydroxytyrosol
Carbamate group
Antitrypanosomal
Antileishmanial
topic Hydroxytyrosol
Carbamate group
Antitrypanosomal
Antileishmanial
description Novel lipophilic hydroxytyrosol N-alkylcarbamate conjugates were synthesized by coupling several alkyl isocyanates of different chain lengths with the primary hydroxy group of this natural phenol. These N-alkylcarbamate conjugates were tested as antitrypanosomal and antileishmanial agents, and their cytotoxicity was evaluated against the human MRC-5 and THP-1 cell lines. Five of these N-alkylcarbamate derivatives showed submicromolar IC concentrations against Trypanosoma brucei brucei, with values ranging from 0.2 to 0.8 μM, and three other hydroxytyrosol conjugates showed IC values below 5 μM. Data for the five most active N-alkylcarbamate derivatives indicate a gain in activity relative to hydroxytyrosol of between 115- and 460-fold, and selectivity indices for control/human MRC-5 cells relative to T. b. brucei parasites of between 47- and 140-fold. These N-alkylcarbamate derivatives were also tested against the intracellular amastigote form of Leishmania donovani in infected THP-1 macrophages, where five compounds had IC values less than or equal to 10 μM, with selectivity indices relative to L. donovani of between 3- and 25-fold in MRC-5 cells and between 8- and 60-fold in THP-1 cells. In all of these derivatives, the ortho-diphenolic groups were free. When the hydroxytyrosol derivatives had ortho-diphenolic groups protected by benzyl groups, cytotoxicity against T. b. brucei and L. donovani showed significantly higher IC values, with most cases exceeding 20 μM.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/389758
url http://hdl.handle.net/10261/389758
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.bioorg.2025.108354
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Academic Press
publisher.none.fl_str_mv Academic Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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