title: Synthesis and bioactivity profile of 5-s-lipoylhydroxytyrosol-based multidefense antioxidants with a sizeable (poly)sulfide chain.
abstract: Novel polyfunctionalized antioxidants, 5-S-lipoylhydroxytyrosol (1) and its disulfide 2, trisulfide 3, and tetrasulfide 4, were prepared from tyrosol and dihydrolipoic acid in the presence, when appropriate, of sulfur. Compound 1 exhibited significant activity in the ferric reducing/antioxidant power (FRAP) assay (1.60 Trolox equiv), whereas polysulfides 2-4 were more efficient in the DPPH reduction assay (88-93% reduction vs 68% by Trolox). At 10 μM concentration, all compounds 1-4 proved to be efficient hydroxyl radical scavengers (56-69% inhibition) in a Fenton reaction assay. When administered to human HepG2 cells, 1-4 proved to be nontoxic and exhibited marked protective effects against reactive oxygen species (ROS) generation (60-84% inhibition at 1 μM concentration) and cell damage induced by 400 μM tert-butylhydroperoxide. All compounds 1-4 exhibited overall greater antioxidant activity than hydroxytyrosol.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Naples, Italy. panzella@unina.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Panzella
authors.forename: Luisella
authors.initials: L
authors.lastname: Verotta
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Martín
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Napolitano
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000975:Antioxidants; C005975:3,4-dihydroxyphenylethanol; C011867:4-hydroxyphenylethanol; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D010626:Phenylethyl Alcohol