Programmable platinum antitumor agents for breast and ovarian cancers

INOR 153

Eunsuk Kim, kime@mit.edu1, Robert G. Croy, rgcroy@mit.edu1, and John M. Essigmann, jessig@mit.edu2. (1) Department of Chemistry and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, (2) Departments of Chemistry and Biological Engineering, Massachusetts Institute of Technology, Room 56-669, 77 Massachusetts Avenue, Cambridge, MA 02139
In order to achieve the selective killing of cancer cells, while minimizing toxicity to normal tissues, we have synthesized (E-en)Pt(II)Cl2, a platinum compound programmed to be selectively toxic in specific cancer cells. The (E-en)Pt(II)Cl2 compound is a bifunctional molecule that consists of ethylendiaminedichloro platinum(II) tethered to the 7-carbon of estradiol. The former is a DNA damaging agent and the latter is a ligand for the estrogen receptor (ER), which is aberrantly expressed in many breast and ovarian cancer cells. The in vitro studies with oligonucleotides, purified ER, and the cell extracts show that (E-en)Pt(II)Cl2 forms DNA adducts that are capable of binding the ER with high affinity. The linker joining the platinum warhead to the ligand has been shown in previous studies to be stable to hydrolytic enzymes. The selective toxicity of (E-en)Pt(II)Cl2 has been observed in various ER positive cancer cells as compared to a control compound.

 

Bioinorganic Chemistry: DNA and RNA
1:30 PM-5:30 PM, Sunday, August 19, 2007 BCEC -- 211, Oral

Division of Inorganic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007