Artículo
Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
Autor/es | Belmonte Reche, Efres
Martínez García, Marta Peñalver, Pablo Gómez Pérez, Verónica Lucas Rodríguez, Ricardo Gamarro, Francisco Pérez Victoria, José María Morales, Juan Carlos |
Departamento | Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica |
Fecha de publicación | 2016 |
Fecha de depósito | 2022-07-08 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Junta de Andalucía |
Identificador del proyecto | FQM-7316
BIO-1786 CTS-7282 |
Cita | Belmonte Reche, E., Martínez García, M., Peñalver, P., Gómez Pérez, V., Lucas Rodríguez, R., Gamarro, F.,...,Morales, J.C. (2016). Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents. European Journal of Medicinal Chemistry, 119, 132-140. |
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