title: DNA metalating-intercalating hybrid agents for the treatment of chemoresistant cancers.
abstract: Nonclassical platinum-based antitumor agents have shown enormous potential in the treatment of chemoresistant cancers. The design of these agents is based on the hypothesis that platinum-containing pharmacophores that react with nuclear DNA in cancer cells radically differently than the clinical agent cisplatin will produce a unique spectrum of biological activity. One such class of molecules are platinum-acridine hybrid agents derived from the prototypical complex [PtCl(en)(ACRAMTU)](NO(3))(2), en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea ("PT-ACRAMTU"). This article summarizes milestones in the development of these agents and reviews critical key concepts that have guided their design and that of related compounds.
authors.affiliation: Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Suryadi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bierbach
mesh_terms: D000166:Acridines / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000737:chemistry* / Q000627:therapeutic use*; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D008958:Models, Molecular; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D018736:DNA Adducts; D007364:Intercalating Agents; D009944:Organoplatinum Compounds; D004247:DNA; D002945:Cisplatin