Potent antioxidant dendrimers lacking pro-oxidant activity

Abstract

It is well known that antioxidants have protective effects against oxidative stress. Unfortunately, in the presence of transition metals, antioxidants including polyphenols with potent antioxidant activities may also exhibit pro-oxidant effects, which may irreversibly damage DNA. Therefore, antioxidants with strong free radical scavenging abilities and devoid of pro-oxidant effects would be of immense biological importance. We report two antioxidant dendrimers with a surface rich in multiple phenolic hydroxyl groups, benzylic hydrogens and electron donating ring substituents that contribute to their potent free radical quenching property. In order to minimize their pro-oxidant effects, the dendrimers were designed with a metal chelating tris(2-aminoethyl)amine (TREN) core. The dendritic antioxidants were prepared by attachment of six syringaldehyde or vanillin molecules to TREN by reductive amination. They exhibited potent radical scavenging properties: 5 times stronger than quercetin and 15 times more potent than Trolox according to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The antioxidant dendrimers also protected low-density lipoprotein, lysozyme and DNA against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced free radical damage. More importantly, unlike quercetin and Trolox, the two TREN antioxidant dendrimers did not damage DNA via their pro-oxidant effects when incubated with physiological amounts of copper ions. The dendrimers also showed no cytotoxicity towards Chinese hamster ovary cells.

Effect of electron donating groups on polyphenol-based antioxidant dendrimers

“…The electrophoretic migration pattern of oxidized LDL is one of the best methods to evaluate the extent of lipoprotein oxidation [23]. We have successfully used a similar strategy for other antioxidants [13,14]. LDL was incubated with 20 mM AAPH and 70 µM dendrimers at 37 °C for 21 h. The lipoproteins were then subjected to agarose electrophoresis.…”

“…A desirable antioxidant should show strong radical scavenging but no pro-oxidant activities. To achieve this goal of designing an ideal antioxidant, we reported synthesis of a new class of antioxidants termed as antioxidant dendrimers [13,14]. The surface of the antioxidant dendrimer is composed of free radical scavenging moieties such as phenolic groups while the core of the dendrimer contains groups that sequester metal ions.…”

Antioxidant activity of some phenolic aldehydes and their diimine derivatives: A DFT study

“…In our present study, we have chosen three plant-based phenolic aldehydes [21][22][23] viz., 3-hydroxybenzaldehyde (I), 3,4-dihydroxybenzaldehyde (II) and vanillin (III), having antioxidant property and designed some diimines [24,25] using three a, x-diamines of different spacer lengths viz., 1,2-diaminoethane (IV), 1,4-diaminobutane (V) and 1,6-diaminohexane (VI) (Scheme 1). We have calculated the O-H bond dissociation energy (BDE) and vertical ionization potentials (IP V ) of these derivatives (Scheme 1).…”

Copper-Granule-Catalyzed Microwave-Assisted Click Synthesis of Polyphenol Dendrimers

“…3 However, when assembled into dendritic forms, the antioxidant activities are remarkably improved. 4,5 …”