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STRUCTURE-ACTIVITY RELATIONSHIPS IN FUNCTIONALIZED PLATINUM-ACRIDINE ANTICANCER AGENTS

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title
STRUCTURE-ACTIVITY RELATIONSHIPS IN FUNCTIONALIZED PLATINUM-ACRIDINE ANTICANCER AGENTS
author
Graham, Leigh Ann
abstract
Since Rosenberg's serendipitous discovery of the cytotoxic properties of cis-diamminedichlor(id)oplatinum(II), better known as cisplatin, the development of new platinum-based chemotherapies with improved activity and reduced toxicity has become a pressing goal. Many second- and third-generation derivatives of cisplatin have been successful in decreasing toxicity, enhancing delivery, and showing a broader spectrum of antitumor activity. Recently, a dual platinating/intercalating DNA-targeted agent, [PtCl(en)(N-[acridin-9-ylamino)ethyl]-N-methylpropionamidine] dinitrate (25), has been reported that shows high activity in NCI-H460 non-small-cell-lung cancer (NSCLC) both in vitro and in vivo, but has proven to have high systemic toxicity (nephrotoxicity). In order to reduce the toxicity of this agent, two new methodologies were developed to reduce unwanted platinum interactions with sulfur-containing biomolecules such as glutathione.
subject
Acridine
Cancer
NSCLC
Platinum
contributor
Bierbach, Ulrich (committee chair)
Cho, Samuel (committee member)
Alexander, Rebecca W (committee member)
Colyer, Christa L (committee member)
Jones, Paul B (committee member)
date
2013-01-09T09:35:12Z (accessioned)
2013-01-09T09:35:12Z (available)
2012 (issued)
degree
Chemistry (discipline)
identifier
http://hdl.handle.net/10339/37655 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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