Unsaturated fatty alcohol derivatives of olive oil phenolic compounds with potential low-density lipoprotein (LDL) antioxidant and antiobesity properties.
A new route for the synthesis of fatty alcohol derivatives of hydroxytyrosol and other olive oil phenolic compounds was developed to allow the preparation of unsaturated derivatives. The biological activity of synthesized compounds was evaluated. Most of the compounds presented a significant antioxidant activity on low-density lipoprotein (LDL) particles. The activity of the tested products was significantly influenced by the number and position of unsaturations as well as modifications on the polar head of the synthesized compounds. Some of them presented modulation of food intake in rats and, due to their molecular similarity with CB(1) endogenous ligands, the endocannabinoid system and PPAR-α were also evaluated as potential targets. The pharmacodynamics could not be totally explained by CB(1) and PPAR-α receptor interactions because only two of the four compounds with biological activity showed a CB(1) activity and all of them presented low PPAR-α affinity, not justifying its whole in vivo activity. The hydroxytyrosol linoleylether (7) increased LDL resistance to oxidation with a capacity similar to that of hydroxytyrosol and was the most active in vivo compound with a hypophagic effect comparable to that of oleoylethanolamine. We consider that this compound could be a good lead compound for future drug development in obesity treatments.
Neurosciences Research Program, IMIM-Hospital del Mar Research Institute, Barcelona, Spain.
Bruno Almeida
BA
Cotrim
Jesús
J
Joglar
M Jesús L
MJ
Rojas
Juan Manuel Decara
JM
del Olmo
Manuel
M
Macias-González
Miguel Romero
MR
Cuevas
Montserrat
M
Fitó
Daniel
D
Muñoz-Aguayo
María Isabel Covas
MI
Planells
Magí
M
Farré
Fernando Rodríguez
FR
de Fonseca
Rafael
R
de la Torre
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002531:Cerebellum / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D000069463:Olive Oil; D047493:PPAR alpha / Q000378:metabolism; D010636:Phenols / Q000737:chemistry*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000737:chemistry; D010938:Plant Oils / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism
D019440:Anti-Obesity Agents; D000975:Antioxidants; D005233:Fatty Alcohols; D008077:Lipoproteins, LDL; D000069463:Olive Oil; D047493:PPAR alpha; D010636:Phenols; D010938:Plant Oils; D043884:Receptor, Cannabinoid, CB1; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol