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

Abstract

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.

Exploring the antioxidant activity of thiaflavan compounds: a quantum chemical study

“…The relevance of the Fe(II)/Fe(III) redox couple in ferrocene is certainly an actor in the efficiency of the T25 thiaflavan system. This has been already suggested by Zai-Qun Liu 59, and Arezki et al 60 who even suggest that the redox couple of Fe(II)/Fe(III) may control the antioxidative property of the molecule 59,60 .…”

Antioxidant Activity and Inhibition of Liver Cancer Cells’ Growth of Extracts from 14 Marine Macroalgae Species of the Mediterranean Sea

“…The ROO • radicals used for DNA damage are usually produced in cells by the reaction of oxygen with radicals containing carbon atoms [ 81 ]. Then, after their entrance to the nucleus, they may cause DNA damage and diseases such as cancer [ 81 ].…”

Multicomponent Reactions for Integrating Multiple Functional Groups into an Antioxidant

“…We have explored the contribution of ferrocene moiety to antioxidative effects and summarized the obtained results in a recently published review. [26]…”

“…In addition, the stoichiometric factor (n) of 131 (5.74) increases to 6.11 of 132 and to 7.12 of 133, revealing that the antioxidative effect of caffeoxyl group in the Passerini 3CR products is dependent upon the increase of the volume of isocyanide moiety. In order to identify this conclusion, as shown as equation (26) in Figure 9, the coumarin moiety is assigned as the isocyanide resource (4-methylcoumarin-7-isocyanide, 134) to perform the Passerini 3CR with acetylized caffeic acid (127) and benzaldehyde (51). The afforded N-(4'-methylcoumarin-7'-yl)-α-caffeoxyl phenylacetamide (135) exerts 8.16 of the stoichiometric factor (n), demonstrating that the antioxidative effect against radical-induced oxidation of DNA can be enhanced by increasing the volume of isocyanide moiety.…”

“…Therefore, ferrocenyl group becomes a novel antioxidative group for protecting DNA against radical‐induced oxidation. We have explored the contribution of ferrocene moiety to antioxidative effects and summarized the obtained results in a recently published review [26] …”