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Chemistry. 2012 Oct 8;18(41):12926-34. doi: 10.1002/chem.201202050. Epub 2012 Sep 17.

DNA metalating-intercalating hybrid agents for the treatment of chemoresistant cancers.

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  • 1Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.


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.

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