Synthesis and evaluation of novel spermidine derivatives as targeted cancer chemotherapeutic agents
| Autor: | Brian D. Thrall, Mahmoud M. Abdel-Monem, Gary G. Meadows, Peter A. Stark |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.drug_class
Cell growth Spermidine Melanoma Experimental Carboxamide Biological activity Antineoplastic Agents chemistry.chemical_compound chemistry Biochemistry Drug Discovery Cancer cell medicine Tumor Cells Cultured Molecular Medicine Moiety Cytotoxicity Polyamine Cell Division Chromatography High Pressure Liquid |
| Zdroj: | Journal of medicinal chemistry. 35(23) |
| ISSN: | 0022-2623 |
| Popis: | The utility of the spermidine moiety as the homing device for the selective delivery of chemotherapeutic and diagnostic agents into cancer cells was explored. Two spermidine analogs containing a cytotoxic agent were synthesized, N-[3,4-bis(benzyloxy)phenethyl]-N alpha-(3-amino-propyl)-L-ornithinamide trihydrochloride, 1a and N-[4-]bis(2-chloroethyl)amino]phenethyl]-N alpha-(3-aminopropyl)-L- ornithinamide tetrahydrochloride, 1b. These compounds were prepared from the fully protected spermidine molecule with a carboxyl group side chain, 8. The ability of the polyamine cytotoxic agents to inhibit B16-BL6 melanoma cell growth in culture was examined. The effects of pretreatment with DFMO on the activity of the synthesized compounds was also studied. The IC50 values of compounds 1a and 1b were on the same order of magnitude as the control compounds, N-acetyldopamine and chlorambucil, respectively. The inhibitory activities of compounds 1a and 1b were not enhanced by pretreatment with DFMO, suggesting that depletion of intracellular polyamines did not enhance the activity of these compounds. |
| Databáze: | OpenAIRE |
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