Enhancing Antioxidant Effect against Peroxyl Radical-Induced Oxidation of DNA: Linking with Ferrocene Moiety!

As a major member in the family of reactive oxygen species, peroxyl radical is able to abstract hydrogen atom from 4-position of ribose, leading to the collapse of DNA strand. Thus, inhibiting oxidative stress with exogenous antioxidants acts as a promising strategy to protect the integrity of DNA structure and is thereby suggested to be a pathway against developments of related diseases. Ferrocene as an organometallic scaffold is widely applied in the design of organometallic drugs, and redox of Fe(II)/Fe(III) in ferrocene offers advantage for providing electron to radicals. Presented herein are our ongoing studies on ferrocene-appended antioxidants, including McMurry reaction applied to construct ferrocifen; Aldol condensation used to prepare ferrocenyl curcumin; Povarov reaction employed to prepare ferrocenyl quinoline; Biginelli reaction used to construct ferrocenyl dihydropyrimidine; Groebke reaction used to synthesize ferrocenyl imidazo[1,2-a]pyridine; and Passerini three-component reaction as well as Ugi four-component reaction applied to synthesize α-acyloxycarboxamide and bisamide, respectively. It is found that ferrocene moiety is able to enhance antioxidative effect of the aforementioned scaffolds even without the aid of phenolic hydroxyl group. The role of ferrocene in enhancing antioxidative effect can be attributable to trapping radicals, decreasing oxidative potential, and increasing the affinity toward DNA strand. Therefore, ferrocene is worthy to be taken into consideration in the design of drugs in relation to DNA oxidation.