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"Design
and Synthesis of Dual-acting Nitroxide-Based Anti-Inflammation Drugs"
Whitney A. Fahrman
Mentor: Dr. Bessie N. A. Mbadugha
St. Mary's College of Maryland, 2004- 2005
Superoxide (SO), which is produced in the metabolism
of oxygen by aerobic cells, causes cell damage and forms reactive
oxygen species (ROS). Inflammation causes the over production of
SO. Superoxide dismutase (SOD) turns superoxide to hydrogen peroxide
and molecular oxygen. Therefore it is beneficial to develop SOD
mimics. Acute and chronic inflammation does not allow SOD to maintain
normal SO levels in the body. From current and past research, investigations
of SOD mimics have turned to nitroxide radicals. Nitroxides can
work intra- and extracellulary to remove SO. They are good candidates
for anti-inflammation drugs because they are nontoxic, metal free,
and they do not cause a high molecular weight when incorporated
into a SOD mimic; therefore, they can penetrate cell membranes.
This study was undertaken to synthesize SOD mimics containing a
nitroxide moiety. Syntheses with the hydroxyl radical scavenger
mannitol were unsuccessful. Synthesis of acetyl maltol and 1-hydroxy-2,2,6,6-tetramethyl-4-piperidinamine
show promising results, as demonstrated by IR and 1H NMR data. However
the obtained product needs to be further purified.
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