title: Selective cytotoxic activity of new lipophilic hydroxytyrosol alkyl ether derivatives.
abstract: Recent data suggest that hydroxytyrosol, a phenolic compound of virgin olive oils, has anticancer activity. This communication reports the synthesis of decyl and hexadecyl hydroxytyrosyl ethers, as well as the cytotoxic activity of hydroxytyrosol and a series of seven hydroxytyrosol alkyl ether derivatives against A549 lung cancer cells and MRC5 non-malignant lung fibroblasts. Hydroxytyrosyl dodecyl ether (HTDE) showed the highest selective cytotoxicity, and possible mechanisms of action were investigated; results suggest that HTDE can moderately inhibit glycolysis, induce oxidative stress, and cause DNA damage in A549 cells. The combination of HTDE with the anticancer drug 5-fluorouracil induced a synergistic cytotoxicity in A549 cancer cells but not in non-malignant MRC5 cells. HTDE also displayed selective cytotoxicity against MCF7 breast cancer cells versus MCF10 normal breast epithelial cells in the 1-30 μM range. These results suggest that the cytotoxicity of HTDE is more potent and selective than that of parent compound hydroxytyrosol.
authors: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville 41012, Spain.
authors: José Manuel
authors: JM
authors: Calderón-Montaño
authors: Andrés
authors: A
authors: Madrona
authors: Estefanía
authors: E
authors: Burgos-Morón
authors: Manuel Luis
authors: ML
authors: Orta
authors: Santiago
authors: S
authors: Mateos
authors: José Luis
authors: JL
authors: Espartero
authors: Miguel
authors: M
authors: López-Lázaro
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004986:Ether / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D015394:Molecular Structure; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D004986:Ether; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol