title: Synthesis and antioxidant evaluation of isochroman-derivatives of hydroxytyrosol: structure-activity relationship.
abstract: Isochroman-derivatives of the natural olive oil phenol hydroxytyrosol (HT) have been synthesised via Oxa-Pictet-Spengler reaction in high yields. Lipophilicity and antioxidant activity were determined to establish the structure-activity relationship of isochromans compared to HT, BHT and α-tocopherol. Antioxidant capacity was tested in two different media: bulk oils, using the Rancimat test, and brain homogenates, by measuring malondialdehyde (MDA) levels as a lipoperoxidation biomarker. In addition, other antioxidant assays (FRAP, ABTS and ORAC) were carried out. Rancimat and MDA results show that antioxidant activity was related with lipophilicity, directly in brain homogenates and inversely in the oils, in agreement with the polar paradox. Free o-diphenolic groups positively determined the activity in the oils, whereas reducing and radical-scavenging activities were related to the number of free hydroxyl moieties. BHT and α-tocopherol showed lower antioxidant activity than isochromans and HT. We conclude that HT-isochromans present significant potential as bioactive compounds.
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), C/José Antonio Nováis 10, 28040 Madrid, Spain. Electronic address: raquel.mateos@ictan.csic.es.
authors.forename: Raquel
authors.initials: R
authors.lastname: Mateos
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, C/Prof. García González 2, Seville, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Madrona
authors.affiliation: IFAPA, Alameda del Obispo, Avda. Menéndez-Pidal s/n, Córdoba, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Pereira-Caro
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, C/Prof. García González 2, Seville, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Domínguez
authors.affiliation: Instituto de la Grasa (CSIC), Avda. Padre García Tejero 4, Sevilla, Spain.
authors.forename: Rosa M A
authors.initials: RM
authors.lastname: Cert
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, University of Seville, C/Prof. García González 2, E-41012 Sevilla, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Parrado
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), C/José Antonio Nováis 10, 28040 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sarriá
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), C/José Antonio Nováis 10, 28040 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, C/Prof. García González 2, Seville, Spain. Electronic address: jles@us.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Espartero
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D010636:Phenols; C005975:3,4-dihydroxyphenylethanol; D008315:Malondialdehyde; D010626:Phenylethyl Alcohol
keywords: Antioxidant activity; Hydroxytyrosol; Lipophilic phenolic antioxidants; Olive oil isochromans; Polar paradox