Iron Depletion Tumor Therapy

Synthesis and Evaluation of Novel Polyaminocarboxylate-Based Antitumor
Agents
J. Med. Chem., 51 (7), 2208–2215, 2008. 10.1021/jm701307j
Hyun-Soon Chong,* Xiang Ma, Haisung Lee, Phuong Bui, Hyun A. Song, and
Noah Birch
Chemistry Division, Biological, Chemical, and Physical Sciences
Department, Illinois Institute of Technology, Chicago, Illinois
Received October 17, 2007
Web Release Date: March 18, 2008

Abstract:
Iron depletion, using iron chelators targeting transferrin receptor
(TfR) and ribonucleotide reductase (RR), is proven to be effective in
the treatment of cancer.
We synthesized and evaluated novel polyaminocarboxylate-based
chelators NETA, NE3TA, and NE3TA-Bn and their bifunctional versions C-
NETA, C-NE3TA, and N-NE3TA for use in iron depletion tumor therapy.
The cytotoxic activities of the novel polyaminocarboxylates were
evaluated in the HeLa and HT29 colon cancer cell lines and compared to
the clinically available iron depletion agent DFO and the frequently
explored polyaminocarboxylate DTPA.
All new chelators except C-NETA displayed enhanced cytotoxicities in
both HeLa and HT29 cancer cells compared to DFO and DTPA.
Incorporation of the nitro functional unit for conjugation to a
targeting moiety into the two potent non-functionalized chelators
NE3TA and NE3TA-Bn (C-NE3TA and N-NE3TA) was well-tolerated and
resulted in a minimal decrease in cytotoxicity. Cellular uptake of C-
NE3TA, examined using a confocal microscope, indicates that the
chelator is taken up into HT29 cancer cells.
Copyright © 2008 American Chemical Society


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