TY - JOUR
T1 - Effect of electron donating groups on polyphenol-based antioxidant dendrimers
AU - Lee, Choon Young
AU - Nanah, Cyprien N.
AU - Held, Rich A.
AU - Clark, Amanda R.
AU - Huynh, Uyen G.T.
AU - Maraskine, Marina C.
AU - Uzarski, Rebecca L.
AU - McCracken, John
AU - Sharma, Ajit
N1 - Funding Information:
This work was supported by Award Number R15GM087697-01 and R15GM087697-01S1 from the National Institute of General Medical Sciences . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health.
Publisher Copyright:
© 2015 Elsevier B.V. and Société Franc¸aise de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
PY - 2015/4
Y1 - 2015/4
N2 - Numerous studies have reported the beneficial effects of antioxidants in human diseases. Among their biological effects, a majority of antioxidants scavenge reactive radicals in the body, thereby reducing oxidative stress that is associated with the pathogenesis of many diseases. Antioxidant dendrimers are a new class of potent antioxidant compounds reported recently. In this study, six polyphenol-based antioxidant dendrimers with or without electron donating groups (methoxy group) were synthesized in order to elucidate the influence of electron donating groups (EDG) on their antioxidant activities. Syringaldehyde (2 ortho methoxy groups), vanillin (1 ortho methoxy group), and 4-hydroxybenzaldehyde (0 methoxy group) were derivatized with propargylamine to form building blocks for the dendrimers. All the six dendrimers contain polyether cores, which were synthesized by attaching pentaerythritol and methyl α-d-glucopyranoside to in-house prepared spacer units. To prepare generation 1 antioxidant dendrimers, microwave energy and granulated metallic copper catalyst were used to link the cores and building blocks together via alkyne-azide 1,3-cycloaddition click chemistry. These reaction conditions resulted in high yields of the target dendrimers that were free from copper contamination. Based on DPPH antioxidant assay, antioxidant dendrimers decorated with syringaldehyde and vanillin exhibited over 70- and 170-fold increase in antioxidant activity compared to syringaldehyde and vanillin, respectively. The antioxidant activity of dendrimers increased with increasing number of EDG groups. Similar results were obtained when the dendrimers were used to protect DNA and human LDL against organic carbon and nitrogen-based free radicals. In addition, the antioxidant dendrimers did not show any pro-oxidant activity on DNA in the presence of physiological amounts of copper. Although the dendrimers showed potent antioxidant activities against carbon and nitrogen free radicals, EPR and DNA protection studies revealed lack of effectiveness of these dendrimers against hydroxyl radicals. The dendrimers were not cytotoxic to CHO-K1 cells.
AB - Numerous studies have reported the beneficial effects of antioxidants in human diseases. Among their biological effects, a majority of antioxidants scavenge reactive radicals in the body, thereby reducing oxidative stress that is associated with the pathogenesis of many diseases. Antioxidant dendrimers are a new class of potent antioxidant compounds reported recently. In this study, six polyphenol-based antioxidant dendrimers with or without electron donating groups (methoxy group) were synthesized in order to elucidate the influence of electron donating groups (EDG) on their antioxidant activities. Syringaldehyde (2 ortho methoxy groups), vanillin (1 ortho methoxy group), and 4-hydroxybenzaldehyde (0 methoxy group) were derivatized with propargylamine to form building blocks for the dendrimers. All the six dendrimers contain polyether cores, which were synthesized by attaching pentaerythritol and methyl α-d-glucopyranoside to in-house prepared spacer units. To prepare generation 1 antioxidant dendrimers, microwave energy and granulated metallic copper catalyst were used to link the cores and building blocks together via alkyne-azide 1,3-cycloaddition click chemistry. These reaction conditions resulted in high yields of the target dendrimers that were free from copper contamination. Based on DPPH antioxidant assay, antioxidant dendrimers decorated with syringaldehyde and vanillin exhibited over 70- and 170-fold increase in antioxidant activity compared to syringaldehyde and vanillin, respectively. The antioxidant activity of dendrimers increased with increasing number of EDG groups. Similar results were obtained when the dendrimers were used to protect DNA and human LDL against organic carbon and nitrogen-based free radicals. In addition, the antioxidant dendrimers did not show any pro-oxidant activity on DNA in the presence of physiological amounts of copper. Although the dendrimers showed potent antioxidant activities against carbon and nitrogen free radicals, EPR and DNA protection studies revealed lack of effectiveness of these dendrimers against hydroxyl radicals. The dendrimers were not cytotoxic to CHO-K1 cells.
KW - Antioxidant
KW - Dendrimer
KW - Electron donating group
KW - Polyphenol
KW - Pro-oxidant
UR - http://www.scopus.com/inward/record.url?scp=84924411109&partnerID=8YFLogxK
U2 - 10.1016/j.biochi.2015.02.001
DO - 10.1016/j.biochi.2015.02.001
M3 - Article
C2 - 25668210
AN - SCOPUS:84924411109
VL - 111
SP - 125
EP - 134
JO - Biochimie
JF - Biochimie
SN - 0300-9084
ER -