Date of Award
Spring 5-2017
Degree Type
Dissertation
Degree Name
Ph.D.
Degree Program
Chemistry
Department
Chemistry
Major Professor
Jursic, Branko
Second Advisor
Trudell, Mark
Third Advisor
Morgan, Lee Roy
Fourth Advisor
Poltavets, Viktor
Abstract
The development of novel targeted therapeutics for the treatment of cancer remains difficult due to the complex nature of the disease itself as well as the challenges associated with the synthesis of these therapeutics. Impediments to the discovery of novel drug candidates include lack of available starting materials and access to well-developed syntheses which are both convenient and economically feasible. Semicarbazides, for instance, are a critical synthon for the manufacture of numerous biologically important molecules. Historically, convenient methods for the synthesis of semicarbazides and their derivatives did not exist. Recently, a facile and efficient method for the preparation of semicarbazides via their corresponding phenyl carbamates was developed. These phenyl carbamate intermediates may also be used to prepare a wide variety of other derivatives such as substituted ureas as well as the aryl carbamoyl derivatives of 1,3-diazinane-5-carboxamide.
While exploring the preparation of the aryl carbamoyl derivatives of 1,3-diazinane-5-carboxamide, it was found that these compounds possess anti-cancer activity against the glioblastoma LN-229 cell line. Intrigued by these results, additional analogues were designed, leading to the development of a small library of chromenopyrimidinedione and pyrimidinequinolinedione compounds as potential anti-cancer agents. Indeed, these two classes of compounds, with many of the derivatives novel, produced a selection of interesting molecules with potent anti-cancer activity against the glioblastoma cell line LN-229 at biologically relevant concentrations. Taken together, these results provide a unique approach not only to the design but also towards the synthesis of novel therapeutics intended for use as anti-cancer agents.
Recommended Citation
Hron, Rebecca, "Design, Synthesis and Glioblastoma Activity of 1,3-Diazinane Based Aryl Amides and Benzo Fused Heterocycles" (2017). University of New Orleans Theses and Dissertations. 2301.
https://scholarworks.uno.edu/td/2301
Supplementary Material II.pdf (31017 kB)
Supplementary Material III.pdf (13634 kB)
Supplementary Material IV.pdf (45121 kB)
Rights
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