Unsaturated Keto and Exomethylene Pyranonucleoside Analogues of Thymine and Uracil Exhibit Potent Antioxidant Properties

Nucleoside analogues play an important role in the development of antitumor and antiviral agents. Specific sugar modified pyranonucleosides, like the keto and exocyclic methylene nucleosides, have been studied for their biological properties, but there is little information regarding their antioxidant activity. The present study reports the antioxidant activity of a series of α,β-unsaturated 2’- or 4’ - keto and exomethylene 5’-hydroxymethyl-lacking pyranonucleosides. The antioxidant activity was evaluated using an in vitro assay which is based on the capacity to protect DNA strand scission induced by peroxyl radicals (ROO?). The majority of the tested nucleoside analogues exhibit potent antioxidant properties against ROO? radicals. We conclude that the presence of a carbon-carbon double bond at α,β-disposition to exomethylene group at position 2 of the sugar moiety and the substitution of thymine with uracil improves the antioxidant capacity of these analogues.