Date of Award
4-20-2010
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Dr. David W. Boykin - Committee Chair
Second Advisor
Dr. Alfons Baumstark - Committee Member
Third Advisor
Dr. W. David Wilson - Committee Member
Abstract
A class of linear diamidines was synthesized for the evaluation as a treatment of Human African Trypanosomiasis. These fused heterocyclic compounds are thiazole[5,4-d]thiazoles and are of interest because the parent compound, 2,5-Bis(4-amidinophenyl)-thiazolo[5,4-d]thiazole HCl salt, which is also called DB 1929, has exhibited a low nanomolar IC50 value against Trypanosoma brucei rhodesiense and has shown selectivity for binding to the human telomere G-quadruplex over that of DNA duplex. A fluoro and a methoxy derivative have been synthesized and are currently undergoing testing for activity and binding affinity. In addition, fluorescence studies of selected diamidines were done to study the effect of structural variation on fluorescence. This data is useful since it can determine what types of moieties are needed to yield a compound that will fluoresce in the higher wavelengths (500 nm and above) of the visible spectrum, which would be advantageous in determining the uptake of the drug in the trypanosome within the endemic areas of Africa with a simple microscope.
DOI
https://doi.org/10.57709/1350365
Recommended Citation
Brown Barber, Jennifer Crystal, "Synthesis of Fused Heterocyclic Diamidines for the Treatment of Human African Trypanosomiasis and Fluorescence Studies of Selected Diamidines." Dissertation, Georgia State University, 2010.
doi: https://doi.org/10.57709/1350365