Date of Award

Spring 5-16-2014

Degree Type

Thesis

Degree Name

Ph.D.

Degree Program

Chemistry

Department

Chemistry

Major Professor

Prof. Branko S. Jursic

Abstract

Telomeres are nucleoprotein complexes found at the ends of linear eukaryotic chromosomes. Telomeres consist of a short sequence of repetitive double stranded DNA, TTAGGG repeats in humans (and all mammals), and a complex of 6 proteins, termed the shelterin complex. The length of the telomeres varies greatly between species, from approximately 300 base pairs in yeast to many 10-15 kilo bases in humans, because of the end replication problem this length get shorten with each cell division and ultimately leads to cell death. However the immortal eukaryotic cells and some transformed human cells over come this incomplete end replication problem with the use of enzyme called Telomerase. Telomerase is a ribonucleoprotein enzyme that adds a specific DNA sequence repeats (TTAGGG) to the 3¢ end of DNA strands in the telomere regions. However from the telomerase activity studies, it was concluded that telomerase is active in almost 90% of human cancers but not in normal somatic tissues. Finally, the low or transient expression of telomerase in normal tissues, including normal stem cells, and the generally longer telomeres in normal cells versus tumor cells provide a degree of tumor specificity to telomerase-based drugs and reduce the probability of toxicity to normal tissue. All of these factors suggest that cancer drugs based on telomerase might have a broad therapeutic window.

This dissertation focusing on the synthesis of acridine derivatives that have the capability to inhibit the enzyme telomerase. Several N-acridyl maleimide (NAM), N-acridyl succinimide (NAS) and N-acridyl phthalimide (NAP) derivatives have been synthesized and evaluated for their anti cancer activity against various cancer cell lines. While synthesizing acridine derivatives it was required to form the C-N bonds at various stages. Developed a copper-nicotinic acid complex, which catalyzes the coupling of aryl halides with N-formyl amines and cyclic imides to form C-N bond. Explored Cu (II) catalyzed formation of C-N bond by coupling aryl halides with various N-nucleophiles such as formamide, N,N-dimethyl formamide, N-formyl amines and various cyclic imides.

Rights

The University of New Orleans and its agents retain the non-exclusive license to archive and make accessible this dissertation or thesis in whole or in part in all forms of media, now or hereafter known. The author retains all other ownership rights to the copyright of the thesis or dissertation.

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