Design, synthesis, and antioxidant activity of FeAOX-6, a novel agent deriving from a molecular combination of the chromanyl and polyisoprenyl moieties.
Several lines of evidence suggest potential benefits by a combination of carotenoids and tocopherols in chronic diseases. Therefore, we have designed FeAOX-6, a novel antioxidant that combines into a single molecule the chroman head of tocopherols and a fragment of lycopene, consisting of a polyisoprenyl sequence of four conjugated double bonds. The ability of FeAOX-6 in inhibiting lipid peroxidation and reactive oxygen species (ROS) production induced by different sources of free radicals (t-BOOH, AAPH, and H2O2) in arachidonic acid solution and in isolated thymocytes was investigated. Its antioxidant efficiency was also compared with that of alpha-tocopherol, lycopene, and a mixture of the two antioxidants. The results strongly suggest that FeAOX-6 can act as a potent antioxidant in our models, by inhibiting malondialdehyde production and ROS generation in a dose- and a time-dependent manner. In the cell model, the compound also provides a higher antioxidant capacity than alpha-tocopherol and lycopene, alone or in combination, suggesting the possibility of an oxidative intramolecular cooperation.
Palozza
Paola
P
Institute of General Pathology, Catholic University, Rome, Italy. p.palozza@rm.unicatt.it
Piccioni
Elisabetta
E
Avanzi
Luca
L
Vertuani
Silvia
S
Calviello
Gabriella
G
Manfredini
Stefano
S
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016718:Arachidonic Acid; D002338:Carotenoids / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D015227:Lipid Peroxidation / Q000187:drug effects; D000077276:Lycopene; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D012996:Solutions; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D024505:Tocopherols / Q000494:pharmacology
D000975:Antioxidants; D002839:Chromans; C480763:FeAOX-6; D017382:Reactive Oxygen Species; D012996:Solutions; D016718:Arachidonic Acid; D002338:Carotenoids; D008315:Malondialdehyde; D024505:Tocopherols; D000077276:Lycopene