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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Chong HS,Ma X,Lee H,Bui P,Song HA,Birch Ndoi
10.1021/jm701307jsubject
Has Abstractpub_date
2008-04-10 00:00:00pages
2208-15issue
7eissn
0022-2623issn
1520-4804journal_volume
51pub_type
杂志文章abstract::Significant efforts have been reported on the development of influenza antivirals including inhibitors of the RNA-dependent RNA polymerase PA N-terminal (PAN) endonuclease. Based on recently identified, highly active metal-binding pharmacophores (MBPs) for PAN endonuclease inhibition, a fragment-based drug development...
journal_title:Journal of medicinal chemistry
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