title: Monofunctional and higher-valent platinum anticancer agents.
abstract: Platinum compounds represent one of the great success stories of metals in medicine. Following the serendipitous discovery of the anticancer activity of cisplatin by Rosenberg, a large number of cisplatin variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. These efforts continue today with increased realization that new strategies are needed to overcome issues of toxicity and resistance inherent to treatment by the approved platinum anticancer agents. One approach has been the use of so-called "non-traditional" platinum(II) and platinum(IV) compounds that violate the structure-activity relationships that governed platinum drug-development research for many years. Another is the use of specialized drug-delivery strategies. Here we describe recent developments from our laboratory involving monofunctional platinum(II) complexes together with a historical account of the manner by which we came to investigate these compounds and their relationship to previously studied molecules. We also discuss work carried out using platinum(IV) prodrugs and the development of nanoconstructs designed to deliver them in vivo.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Johnstone
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D015394:Molecular Structure; D036103:Nanotechnology / Q000379:methods; D009584:Nitrogen; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D009584:Nitrogen; D002945:Cisplatin