Date of Award

Spring 5-19-2017

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.

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.

Available for download on Thursday, May 19, 2022

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