Abstract
| - In this paper we describe the synthesis and characterization of a series of simple spermine/amino acid conjugates, some of which potently inhibit the uptake of spermidine into MDA-MB-231 breast cancer cells. The presence of an amide in the functionalized polyamine appearedto add to the affinity for the polyamine transporter. The extensive biological characterizationof an especially potent analogue from this series, the Lys-Spm conjugate (31), showed thismolecule will be an extremely useful tool for use in polyamine research. It was shown that theuse of 31 in combination with DFMO led to a cytostatic growth inhibition of a variety of cancercells, even when used in the presence of an extracellular source of transportable spermidine.It was furthermore shown that this combination effectively reduced the cellular levels ofputrescine and spermidine while not affecting the levels of spermine. These facts together withthe nontoxic nature of 31 make it a novel lead for further anticancer development.
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