STRUCTURE-ACTIVITY RELATIONSHIPS IN FUNCTIONALIZED PLATINUM-ACRIDINE ANTICANCER AGENTS

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.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2012

Author dc:creator

• Graham, Leigh Ann

• Acridine

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/37655

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/37655