{"id":{"repo_id":"wfu","oai_identifier":"oai:wakespace.lib.wfu.edu:10339/37655"},"canonical_url":"https://search.dev.ndltd.org/etd/wfu/oai:wakespace.lib.wfu.edu:10339/37655","repository":{"repo_id":"wfu","name":"Wake Forest University","base_url":"https://wakespace.lib.wfu.edu/oai/request"},"display":{"title":"STRUCTURE-ACTIVITY RELATIONSHIPS IN FUNCTIONALIZED PLATINUM-ACRIDINE ANTICANCER AGENTS","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Graham, Leigh Ann"],"institution":"Wake Forest University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012","date_published":"2012","updated_at":"2026-07-27T22:01:33Z","subjects":["Acridine"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10339/37655","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Graham, Leigh Ann"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2013-01-09T09:35:12Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2013-01-09T09:35:12Z"]},{"key":"dc:date.issued","label":"Date","values":["2012"]},{"key":"dc:publisher","label":"Institution","values":["Wake Forest University"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Acridine"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10339/37655"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:title","label":"Title","values":["STRUCTURE-ACTIVITY RELATIONSHIPS IN FUNCTIONALIZED PLATINUM-ACRIDINE ANTICANCER AGENTS"]}]}],"canonical_facts":{"dc:creator":["Graham, Leigh Ann"],"dc:date.accessioned":["2013-01-09T09:35:12Z"],"dc:date.available":["2013-01-09T09:35:12Z"],"dc:date.issued":["2012"],"dc:description.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."],"dc:identifier.uri":["http://hdl.handle.net/10339/37655"],"dc:language.iso":["en"],"dc:publisher":["Wake Forest University"],"dc:subject":["Acridine"],"dc:title":["STRUCTURE-ACTIVITY RELATIONSHIPS IN FUNCTIONALIZED PLATINUM-ACRIDINE ANTICANCER AGENTS"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T22:01:33Z"}