2024-03-28T15:52:19Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1634812021-05-24T10:40:43Zcom_10261_64com_10261_1col_10261_317
Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
Belmonte-Reche, Efres
Martínez-García, Marta
Peñalver, Pablo
Gómez-Pérez, Veronica
Lucas, Ricardo
Gamarro, Francisco
Pérez-Victoria, J. M.
Morales, Juan C.
Antileishmanial
Antitrypanosomal
Hydroxytyrosol
Tyrosol
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.
We gratefully acknowledge to Junta de Andalucía (Grant No. FQM-7316 (JCM), BIO-1786 (JMPV), CTS-7282 (FG)) and Spanish Ministry of Economy and Competitiveness (Grant No. SAF2011-28215 (JMPV) and SAF2012-34267 (FG)) for financial support.
Peer reviewed
2018-04-11T10:34:58Z
2018-04-11T10:34:58Z
2016-08-25
preprint
http://purl.org/coar/resource_type/c_816b
European Journal of Medicinal Chemistry
0223-5234
http://hdl.handle.net/10261/163481
10.1016/j.ejmech.2016.04.047
1768-3254
en
Preprint
www.sciencedirect.com/science/article/pii/S0223523416303403?via%3Dihub
Sí
open
Elsevier