The overproduction of reactive oxygen species (ROS) have been linked to
diseases and other pathologies. As therapeutic agents, antioxidants have been tested and
some shown to attenuate these diseases by relieving oxidative stress. The May laboratory
has previously developed a family of phenylaminoalkyl selenides and has demonstrated
the antihypertensive and antioxidant properties of these compounds.
To further understand the antioxidant property of these selenide compounds, the
two step mechanism of the reaction between the selenoxide form and glutathione was
investigated by stopped-flow and mass spectrometry, leading to the detection and
characterization of a novel thioselenurane intermediate. Mass spectrometry studies
supported the redox cycle of the selenide compounds as a straightforward cycle with no
byproducts or side reactions and was the first evidence reported of a thioselenurane
intermediate present in a reduction reaction of a selenoxide.
The therapeutic potential of these compounds was further supported by cell and
histological studies demonstrating their ability to alleviate the cardiotoxic effect of
anthracyclines without affecting the anti-cancer property of the drugs. Codosage of a
phenylaminoethyl selenide with Doxorubicin decreased the infiltration of inflammation
cells in the myocardium of mice. Phenylaminoethyl selenides were also able to maintain
the body weight of mice treated with Doxorubicin, compared to mice treated with
Doxorubicin alone.
In order to make the possibility of using Phenylaminoalkyl selenides as
therapeutic agents or supplements with other agents, delivery of the compounds was
investigated. N acetyl phenylaminoethyl selenides were successfully encapsulated into
poly(lactic-co-glycolic) (PLGA) nanoparticles using the nanoprecipitation technique. An
attempt was made to demonstrate the ability of these selenide- nanoparticles to reduce
cellular oxidative stress caused by incubation with LPS. Future studies are needed to
optimize the loading of the selenide compounds into nanocarriers and to demonstrate the
ability of the encapsulated drug to work as the free drug. The long term goal of this
research is to fully understand the potential of phenylaminoalkyl selenides as an efficient
therapeutic agent for ailments derived from increased levels of ROS and a state of
oxidative stress.
As a supplemental project funded by the National Science Foundation, the Center
for Innovative Biomaterial Education and Research (CIBER) was created. Enzymatically
catalyzed reaction and polymerizations were investigated using Candida antarctica
Lipase B (CALB). Several CALB catalyzed Michael addition reactions were successful
and yielded compounds that could be used as future reactants and monomers. As an
education requirement of the project a website was created in order to educate the public
of the importance, sources and uses of biomaterials. The website provides information
for all levels of students and educators. This center has allowed The Georgia Institute of
Technology to form relationships and exchange programs with leading universities
around the world allowing the exchange of knowledge and research in biomaterials.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/42937 |
| Date | 16 November 2011 |
| Creators | Cowan, Elizabeth Alice |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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