Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents

Trypanosomiasis and leishmaniasis keep being a real challenge for health and development of African countries. Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR)...

ver descrição completa

Detalhes bibliográficos
Autores: Belmonte Reche, Efres, Martínez García, Marta, Peñalver, Pablo, Gómez Pérez, Verónica, Lucas Rodríguez, Ricardo, Gamarro, Francisco, Pérez Victoria, José María, Morales, Juan Carlos
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2016
País:España
Recursos:Universidad de Sevilla (US)
Repositório:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/135176
Acesso em linha:https://hdl.handle.net/11441/135176
https://doi.org/10.1016/j.ejmech.2016.04.047
Access Level:Acceso aberto
Palavra-chave:Antileishmanial
Antitrypanosomal
Hydroxytyrosol
Tyrosol
id ES_d60e6b75dfaec54e20da84c404ad6c29
oai_identifier_str oai:idus.us.es:11441/135176
network_acronym_str ES
network_name_str España
repository_id_str
spelling Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agentsBelmonte Reche, EfresMartínez García, MartaPeñalver, PabloGómez Pérez, VerónicaLucas Rodríguez, RicardoGamarro, FranciscoPérez Victoria, José MaríaMorales, Juan CarlosAntileishmanialAntitrypanosomalHydroxytyrosolTyrosolTrypanosomiasis and leishmaniasis keep being a real challenge for health and development of African countries. Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR) and hydroxytyrosol (HT) and several of their esters and metabolites. We found significant IC50 values against Trypanosoma brucei for HT decanoate ester and HT dodecanoate ester (0.6 and 0.36 μM, respectively). This represents a large increase in activity with respect to HT (79 and 132 fold, respectively). Moreover, both compounds displayed a high selectivity index against MRC-5, a non-tumoral human cell line (118 and 106, respectively). Then, we synthesized a focused library of compounds to explore structure-activity. We found the ether and thiourea analogs of HT decanoate ester and HT dodecanoate ester also showed IC50 values against T. brucei in the low micromolar range. In conclusion, the di-ortho phenolic ring and medium size alkyl chain are essential for activity whereas the nature of the chemical bond among them seems less important.Junta de Andalucía FQM-7316, BIO-1786, CTS-7282ElsevierQuímica Orgánica y FarmacéuticaJunta de Andalucía2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/135176https://doi.org/10.1016/j.ejmech.2016.04.047reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésEuropean Journal of Medicinal Chemistry, 119, 132-140.FQM-7316BIO-1786CTS-7282https://doi.org/10.1016/j.ejmech.2016.04.047info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1351762026-06-17T12:51:07Z
dc.title.none.fl_str_mv Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
title Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
spellingShingle Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
Belmonte Reche, Efres
Antileishmanial
Antitrypanosomal
Hydroxytyrosol
Tyrosol
title_short Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
title_full Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
title_fullStr Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
title_full_unstemmed Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
title_sort Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
dc.creator.none.fl_str_mv Belmonte Reche, Efres
Martínez García, Marta
Peñalver, Pablo
Gómez Pérez, Verónica
Lucas Rodríguez, Ricardo
Gamarro, Francisco
Pérez Victoria, José María
Morales, Juan Carlos
author Belmonte Reche, Efres
author_facet Belmonte Reche, Efres
Martínez García, Marta
Peñalver, Pablo
Gómez Pérez, Verónica
Lucas Rodríguez, Ricardo
Gamarro, Francisco
Pérez Victoria, José María
Morales, Juan Carlos
author_role author
author2 Martínez García, Marta
Peñalver, Pablo
Gómez Pérez, Verónica
Lucas Rodríguez, Ricardo
Gamarro, Francisco
Pérez Victoria, José María
Morales, Juan Carlos
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Química Orgánica y Farmacéutica
Junta de Andalucía
dc.subject.none.fl_str_mv Antileishmanial
Antitrypanosomal
Hydroxytyrosol
Tyrosol
topic Antileishmanial
Antitrypanosomal
Hydroxytyrosol
Tyrosol
description Trypanosomiasis and leishmaniasis keep being a real challenge for health and development of African countries. Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR) and hydroxytyrosol (HT) and several of their esters and metabolites. We found significant IC50 values against Trypanosoma brucei for HT decanoate ester and HT dodecanoate ester (0.6 and 0.36 μM, respectively). This represents a large increase in activity with respect to HT (79 and 132 fold, respectively). Moreover, both compounds displayed a high selectivity index against MRC-5, a non-tumoral human cell line (118 and 106, respectively). Then, we synthesized a focused library of compounds to explore structure-activity. We found the ether and thiourea analogs of HT decanoate ester and HT dodecanoate ester also showed IC50 values against T. brucei in the low micromolar range. In conclusion, the di-ortho phenolic ring and medium size alkyl chain are essential for activity whereas the nature of the chemical bond among them seems less important.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/135176
https://doi.org/10.1016/j.ejmech.2016.04.047
url https://hdl.handle.net/11441/135176
https://doi.org/10.1016/j.ejmech.2016.04.047
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv European Journal of Medicinal Chemistry, 119, 132-140.
FQM-7316
BIO-1786
CTS-7282
https://doi.org/10.1016/j.ejmech.2016.04.047
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420803272998912
score 15,301629

Registros relacionados