Amino acid/spermine conjugates: polyamine amides as potent spermidine uptake inhibitors
| Autor: | Scott M. Vanderwerf, Feng Cai, Gerard F. Graminski, and Heather K. Webb, C. Lance Carlson, Reitha S. Weeks, Josh R. Ziemer, Mark R. Burns |
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| Rok vydání: | 2001 |
| Předmět: |
Eflornithine
Spermidine Spermine Antineoplastic Agents chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Putrescine Tumor Cells Cultured Structure–activity relationship Humans Drug Interactions Amino Acids chemistry.chemical_classification Lysine Biological Transport Ornithine Decarboxylase Inhibitors Amino acid chemistry Biochemistry Ornithine Decarboxylase Inhibitor Molecular Medicine Growth inhibition Drug Screening Assays Antitumor Polyamine |
| Zdroj: | Journal of medicinal chemistry. 44(22) |
| ISSN: | 0022-2623 |
| Popis: | 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 appeared to add to the affinity for the polyamine transporter. The extensive biological characterization of an especially potent analogue from this series, the Lys-Spm conjugate (31), showed this molecule will be an extremely useful tool for use in polyamine research. It was shown that the use of 31 in combination with DFMO led to a cytostatic growth inhibition of a variety of cancer cells, 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 of putrescine and spermidine while not affecting the levels of spermine. These facts together with the nontoxic nature of 31 make it a novel lead for further anticancer development. |
| Databáze: | OpenAIRE |
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