Synthesis, radiosynthesis, and biological evaluation of new proteasome inhibitors in a tumor targeting approach.

Abstract

Proteasome inhibition is a new strategy in cancer therapy. We synthesized three new peptide aldehyde inhibitors linked to the benzamide derivative structure to use their cytotoxic activity against malignant melanoma cells. Of these, 10 displayed the highest cytotoxicity (0.18 +/- 0.16 microM). A radiosynthesis of the iodine aldehyde was performed. Its drug biodistribution showed that some selectivity of the benzamide group toward malignant melanoma tissue was conserved.

• Authors: Magali Vivier, Maryse Rapp, Janine Papon, Pierre Labarre, Marie-Josephe Galmier, Jacques Sauzière, Jean-Claude Madelmont
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 4 Pg. 1043-7 (Feb 28 2008) ISSN: 0022-2623 [Print] United States
• PMID: 18237109 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzamides
• Iodine Radioisotopes
• N(4)-(2-(diethylamino)ethyl)-2-iodo-N(1)-(4-methyl-1-(4-methyl-1-(4-methyl-1-oxopentan-2-ylamino)-1-oxopentan-2-ylamino)-1-oxopentan-2-yl)terephthalamide
• Oligopeptides
• Phthalic Acids
• Proteasome Inhibitors
• Radiopharmaceuticals
• Triazenes
• Leucine

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacokinetics, pharmacology)
• Benzamides (chemical synthesis, pharmacokinetics, pharmacology)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Humans
• Iodine Radioisotopes
• Leucine (analogs & derivatives, chemical synthesis, pharmacokinetics, pharmacology)
• Melanoma, Experimental (metabolism)
• Mice
• Neoplasm Transplantation
• Oligopeptides (chemical synthesis, pharmacokinetics, pharmacology)
• Phthalic Acids (chemical synthesis, pharmacokinetics, pharmacology)
• Proteasome Inhibitors
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics, pharmacology)
• Stereoisomerism
• Tissue Distribution
• Transplantation, Heterologous
• Triazenes (chemical synthesis, pharmacokinetics, pharmacology)