{"id":4923,"date":"2014-06-05T12:11:20","date_gmt":"2014-06-05T16:11:20","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?page_id=4923"},"modified":"2014-06-05T12:11:20","modified_gmt":"2014-06-05T16:11:20","slug":"williams","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/riinbre\/research\/surf-training-award\/williams\/","title":{"rendered":"Synthesis and screening of selective anti-cancer and cell-imaging agents"},"content":{"rendered":"<p><strong>Investigator:<\/strong>\u00a0John Williams Jr., Rhode Island College<\/p>\n<p><strong>Scientific Theme:<\/strong>\u00a0Cancer<\/p>\n<p style=\"text-align: justify\"><strong>Abstract:\u00a0<\/strong>Arylphosphonium salts (APS) are cytotoxic lipophilic cations that can cross cell membranes. They interact\u00a0with DNA, both nuclear and mitochondrial, and can block the replication fork. They are antibacterial and\u00a0antifungal by unknown mechanism(s). Some are active against cancer cells in culture and in vivo. These\u00a0salts are preferentially taken up by malignant cells and by mitochondria in normal cells. They have been\u00a0used as carrier molecules to deliver DNA-alkylating agents into mitochondria. Some of these compounds\u00a0are inherently fluorescent. They can also be conjugated with a flurophore to enhance fluorescence and cell\u00a0imaging. We have synthesized some of these compounds and observed these effects in our laboratories.\u00a0We will synthesize and purify by HPLC a library of new examples of these compounds for anti-cancer\u00a0screening by collaborators here and at other institutions. Three to five step high-yield protocols developed in\u00a0our laboratories using readily available reagents, microwave-assisted and\/or solvent-free synthesis will be\u00a0employed. Compounds will be tested in cell-imaging and cell toxicity studies, in fluorescence assays, and\u00a0DNA replication-blocking experiments to gain insight into the mechanism(s) of their anti-cancer activity and\u00a0general toxicity. Leads discovered in screening will be modified to increase potency to sub-micromolar\u00a0activity. They will be tested for binding to both ds and G4 DNA by CD and ITC experiments.\u00a0Up to four students can be involved directly in this project during the first year. Success at any level in any of\u00a0the research areas will provide opportunities for more students to continue this work in subsequent years.<\/p>\n<p style=\"text-align: justify\"><strong>Human Health Relevance:<\/strong>\u00a0Cancer therapy, early cancer diagnosis, breast cancer, cell-imaging, cell targeting, medicinal chemistry,\u00a0computational medicinal chemistry, dsDNA toxicity, G4 DNA toxicity, selective drug uptake, blocking of DNA\u00a0amplification, fluroescence labeling, mechanisms of antiproliferation agents, correlations for and predictors of\u00a0anti-cancer activity, green chemistry, microwave assisted synthesis, computational screening, in vitro\u00a0screening.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigator:\u00a0John Williams Jr., Rhode Island College Scientific Theme:\u00a0Cancer Abstract:\u00a0Arylphosphonium salts (APS) are cytotoxic lipophilic cations that can cross cell membranes. They interact\u00a0with DNA, both nuclear and mitochondrial, and can block the replication fork. They are antibacterial and\u00a0antifungal by unknown mechanism(s). Some are active against cancer cells in culture and in vivo. These\u00a0salts are preferentially taken [&hellip;]<\/p>\n","protected":false},"author":1036,"featured_media":0,"parent":10206,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-twocol.php","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-4923","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4923","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/1036"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=4923"}],"version-history":[{"count":0,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4923\/revisions"}],"up":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/10206"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=4923"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}