Potent antioxidant dendrimers lacking pro-oxidant activity.
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 properties. 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 assay. The antioxidant dendrimers also protected low-density lipoprotein, lysozyme, and DNA against 2,2'-azobis(2-amidinopropane) dihydrochloride-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 toward Chinese hamster ovary cells.
Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859, USA. lee1cy@cmich.edu
Choon Young
CY
Lee
Ajit
A
Sharma
Rebecca L
RL
Uzarski
Jae Eun
JE
Cheong
Hao
H
Xu
Rich A
RA
Held
Samik K
SK
Upadhaya
Julie L
JL
Nelson
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects; D050091:Dendrimers; D004587:Electrophoresis, Agar Gel; D009682:Magnetic Resonance Spectroscopy; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000975:Antioxidants; D050091:Dendrimers; D017382:Reactive Oxygen Species; D004247:DNA