Development of Polyamine Transport Ligands with Improved Metabolic Stability and Selectivity against Specific Human Cancers
Abbreviated Journal Title
J. Med. Chem.
Keywords
HUMAN-MELANOMA CELLS; HAMSTER OVARY CELLS; BIOLOGICAL EVALUATION; MAMMALIAN-CELLS; MOLECULAR REQUIREMENTS; SPERMINE ANALOGS; EFFICIENT; PROLIFERATION; CYTOTOXICITY; RECOGNITION; Chemistry, Medicinal
Abstract
Polyamine homeostasis is critical for life and is accomplished via a balance of polyamine biosynthesis, degradation, and transport. Rapidly dividing cancer cells have been shown to have high polyamine transport activity compared to normal cells, likely due to their high requirement for polyamine metabolites. The polyamine transport system (PTS) is a therapeutically relevant target, as it can provide selective drug delivery to cancer cells. This report describes the synthesis and biological evaluation of multimeric polyamine derivatives as efficient PTS ligands. Arylmethyl-polyamine derivatives were synthesized to address two important concerns in PTS drug design: (a) PTS selectivity and (b) stability to amine oxidases. N-1,N-1'-[Naphthalene-1,4-diylbis(methylene)]bis{N-4-[4-(methylamino)butyl])-butane-1,4-diamine}, 3b, was found to have an optimal balance between these parameters and demonstrated excellent targeting of melanoma (e.g., MALME-3M) and breast cancer cells (e.g., T47D) over other cancer cell lines. These results provide a method to selectively target cancers via their intrinsic need for polyamine metabolites.
Journal Title
Journal of Medicinal Chemistry
Volume
56
Issue/Number
14
Publication Date
1-1-2013
Document Type
Article
DOI Link
Language
English
First Page
5819
Last Page
5828
WOS Identifier
ISSN
0022-2623
Recommended Citation
"Development of Polyamine Transport Ligands with Improved Metabolic Stability and Selectivity against Specific Human Cancers" (2013). Faculty Bibliography 2010s. 4447.
https://stars.library.ucf.edu/facultybib2010/4447
Comments
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