Antioxidants have been reported to be beneficial for prevention of a variety of human diseases including cancer and cardiovascular, neurodegenerative, pulmonary and chronic ailments. Commonly available antioxidants are small molecular weight compounds that have the ability to neutralize free radicals, destroy potential radical forming substances, boost the immune system and exhibit other biological activities that are beneficial to human health. Little is known about large antioxidant molecules with molecular weights in the thousands. More specifically, the biological effects of dendritic forms of antioxidants have not been reported before. This application involves the synthesis of antioxidant dendrimers composed of numerous units of antioxidants connected to one another in a tree like fashion so that they can effectively scavenge free radicals. The nano-antioxidant molecules will be synthesized with dihydroxybenzaldehyde building blocks and propargylamine branching units in a reiterative manner to give well-defined and precise dendrimers. It is hypothesized that this unique antioxidant architecture will display cooperative effects and reveal some interesting and beneficial properties such as improved aqueous solubility and stability and enhanced radical scavenging potency. It is also believed that these nano-particles will have stronger interactions with biomolecules and therefore be better protectants than small molecule antioxidants against free radical damage. These novel nano-materials will be characterized by a number of chemical and bio-analytical techniques including polyacrylamide gel electrophoresis, HPLC, spectroscopy and mass spectrometry. Their antioxidant potency will be measured with electron spin resonance and spectroscopic assays and compared to controls, such as their monomeric counterparts (building block) and common antioxidants like vitamins C and E. The ability of the antioxidant dendrimers to protect DNA, lipids, proteins and red blood cells will be determined in a free radical generating system in vitro and compared to small molecule antioxidants. DNA strand breakage will be determined by agarose gel electrophoresis. Protein damage will be monitored by fluorescence spectroscopy, reversed phase HPLC, size exclusion chromatography, and gel electrophoresis. Lipid peroxidation will be measured by monitoring diene formation with ultraviolet spectrophotometry while cell damage will be evaluated by red blood cell hemolysis. These studies should provide invaluable data towards the protective effects of nano-antioxidants on biomolecules and cells. In addition, the proposed antioxidant dendrimer will provide a unique platform for preparing multifunctional nano-devices for detection, diagnosis and treatment of diseases.
This application will involve the synthesis of antioxidant dendrimers and investigate their free radical scavenging potency as well as their effects on biomolecules and cells. Results of this study will benefit the use of nano-antioxidants for prevention, detection, diagnosis and treatment of human diseases that have a strong association with oxidative stress including cancer, cardiovascular diseases, and chronic inflammatory and neurodegenerative diseases.
| Lee, Choon Young; Nanah, Cyprien N; Held, Rich A et al. (2015) Effect of electron donating groups on polyphenol-based antioxidant dendrimers. Biochimie 111:125-34 |
| Lee, Choon Young; Held, Rich; Sharma, Ajit et al. (2013) Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol dendrimers. J Org Chem 78:11221-8 |
| Lee, Choon Young; Sharma, Ajit; Uzarski, Rebecca L et al. (2011) Potent antioxidant dendrimers lacking pro-oxidant activity. Free Radic Biol Med 50:918-25 |
| Lee, Choon Young; Sharma, Ajit; Cheong, Jae Eun et al. (2009) Synthesis and antioxidant properties of dendritic polyphenols. Bioorg Med Chem Lett 19:6326-30 |
