2. Academic Validation
  3. Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents

Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents

  • Eur J Med Chem. 2016 Aug 25:119:132-40. doi: 10.1016/j.ejmech.2016.04.047.
Efres Belmonte-Reche 1,  Marta Martínez-García 1,  Pablo Peñalver 2,  Verónica Gómez-Pérez 1,  Ricardo Lucas 2,  Francisco Gamarro 1,  José María Pérez-Victoria 3,  Juan Carlos Morales 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, PTS Granada, Avda. del Conocimiento, 17, 18016, Armilla, Granada, Spain.
  • 2 Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, PTS Granada, Avda. del Conocimiento, 17, 18016, Armilla, Granada, Spain; Department of Bioorganic Chemistry, Institute of Chemical Research, CSIC - University of Seville, Avda. Americo Vespucio, 49, 41092, Sevilla, Spain.
  • 3 Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, PTS Granada, Avda. del Conocimiento, 17, 18016, Armilla, Granada, Spain. Electronic address: josepv@ipb.csic.es.
  • 4 Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, PTS Granada, Avda. del Conocimiento, 17, 18016, Armilla, Granada, Spain; Department of Bioorganic Chemistry, Institute of Chemical Research, CSIC - University of Seville, Avda. Americo Vespucio, 49, 41092, Sevilla, Spain. Electronic address: jcmorales@ipb.csic.es.
PMID: 27155468 DOI: 10.1016/j.ejmech.2016.04.047
Abstract

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.

Keywords

Antileishmanial; Antitrypanosomal; Hydroxytyrosol; Tyrosol.

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