Unsaturated Fatty Alcohol Derivatives of Olive Oil Phenolic Compounds with Potential Low-Density Lipoprotein (LDL) Antioxidant and Antiobesity Properties

• Published in: Journal of agricultural and food chemistry Vol. 60; no. 4; pp. 1067 - 1074
• Main Authors: Cotrim, Bruno Almeida, Joglar, Jesús, Rojas, M. Jesús L, del Olmo, Juan Manuel Decara, Macias-González, Manuel, Cuevas, Miguel Romero, Fitó, Montserrat, Muñoz-Aguayo, Daniel, Covas Planells, María Isabel, Farré, Magí, Rodríguez de Fonseca, Fernando, de la Torre, Rafael
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.02.2012; Amer Chemical Soc
• Subjects: Agriculture; Agriculture, Multidisciplinary; alcohols; Animals; Anti-Obesity Agents - pharmacology; antioxidant activity; Antioxidants - pharmacology; Biological and medical sciences; Cerebellum - metabolism; Chemistry; Chemistry, Applied; drugs; Eating - drug effects; Fat industries; Fatty Alcohols - chemistry; Fatty Alcohols - pharmacology; Feeding. Feeding behavior; Food industries; food intake; Food Science & Technology; Fundamental and applied biological sciences. Psychology; Life Sciences & Biomedicine; Lipid Peroxidation - drug effects; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - drug effects; low density lipoprotein; Male; obesity; Olive Oil; oxidation; phenolic compounds; Phenols - chemistry; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - chemistry; Physical Sciences; Plant Oils - chemistry; PPAR alpha - metabolism; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - metabolism; Science & Technology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; CB1; ether; PPAR-α; fatty alcohol; obesity; OXIDATION; ACTIVATION; NUCLEAR; RECEPTOR; OLEOYLETHANOLAMIDE; ALKYL HYDROXYTYROSYL ETHERS; METABOLISM; INVERSE-AGONIST; PPAR-alpha; Obesity; Ether; Nutrition disorder; Vegetable oil; Olive oil; Edible oil; Antioxidant; Properties; Lipoprotein LDL; Fatty alcohol; Phenols; Nutritional status; CB
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf203814r

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 CB1 endogenous ligands, the endocannabinoid system and PPAR-α were also evaluated as potential targets. The pharmacodynamics could not be totally explained by CB1 and PPAR-α receptor interactions because only two of the four compounds with biological activity showed a CB1 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.