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dc.contributor.advisorGreen, Kayla
dc.contributor.authorSadagopan, Nishu
dc.date2021-05-19
dc.date.accessioned2021-10-25T21:48:49Z
dc.date.available2021-10-25T21:48:49Z
dc.date.issued2021
dc.identifier.urihttps://repository.tcu.edu/handle/116099117/49087
dc.description.abstractAlzheimer's disease is a neurodegenerative disorder that is characterized by amyloid-beta plaques, neurofibrillary tangles, and unregulated reactive oxygen species. The production of reactive oxygen species in the brain is exacerbated by an excess of free-metal ions in nervous tissue. Our team and others have shown a library of tetra-azamacrocycles to have the ability to scavenge free-metal ions and quench reactive oxygen species. These macrocyclic ligands have, thus, been considered as potential therapeutic agents for combatting Alzheimer's disease. The ability of a neuro-active pharmaceutical to cross the blood-brain barrier is crucial to its pharmacological success and has proven to be a significant challenge to date in moving molecules from the bench to clinical treatment paradigms. The aim of this work is to enhance the pharmacological potential of these macrocyclic ligands. To accomplish this, computational analyses were performed on two tetra-azamacrocycles to predict their baseline blood-brain barrier permeability. The structures of these macrocycles were then modified with various moieties and analyzed via the same computational methods to predict their blood-brain barrier permeability potential. One target modification this project is focused on is the attachment of omega-3 fatty acids to these tetra-azamacrocycles. Omega-3 fatty acids have been shown to have beneficial anti-inflammatory properties in vivo and have the ability to assist in transporting molecules across the blood-brain barrier. Thus, the inclusion of these moieties to the structure of the Green Group ligands are attractive in regard to enhancing their pharmacological potential. To accomplish this attachment, the synthetic approach of one of the Green Group's flagship tetra-azamacrocycles, OHPyN3, had to be completely reimagined. New synthetic approaches and protection strategies were employed to achieve a suitable intermediate molecule primed for the addition omega-3 fatty acids. These novel synthetic methods and subsequent results are discussed in this work herein.
dc.subjectAlzheimer's disease
dc.subjectmacrocycles
dc.subjectomega-3 fatty acids
dc.subjectreactive oxygen species
dc.subjectchelation
dc.subjectblood-brain barrier
dc.titleEnhancing the therapeutic potential of heterocyclic ligands for treating Alzheimer's disease
etd.degree.departmentChemistry
local.collegeCollege of Science and Engineering
local.collegeJohn V. Roach Honors College
local.departmentChemistry and Biochemistry


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