New aldehyde and vinylsulfone proteasome inhibitors for targeted melanoma therapy.

Abstract

The proteasome is a promising target in cancer therapy. However, it is ubiquitous and its inhibitors cause side effects. To target melanoma cells we synthesized new peptide aldehyde and vinylsulfone inhibitors of the proteasome conjugated to the melanin-targeting ligand (MTL) derived from radiotracer [(123)I]-N-(2-diethylaminoethyl)benzamide ([(123)I]BZA) or [(125)I]-N-(4-dipropylaminobutyl)-4-iodobenzamide ([(125)I]BZ18). Influence on the cytotoxicity of the benzamide alkyl side chain length and the composition of the amino acid sequence was assessed. Among the conjugates evaluated, compound 16 and 22 presented the highest cytotoxicity (IC(50), 0.71 and 0.64 μM respectively), which persisted in the presence of an MTL derived from N-(dialkylaminoalkylenyl)benzamide residue.

• Authors: Magali Vivier, Maryse Rapp, Marie-Josephe Galmier, Anne-Sophie Jarrousse, Elisabeth Miot-Noirault, Fernand Leal, Valérie Weber, Jacques Métin, Jacques Sauzière, Jean-Michel Chezal, Jean-Claude Madelmont
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 46 Issue 11 Pg. 5705-10 (Nov 2011) ISSN: 1768-3254 [Electronic] France
• PMID: 21924528 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Chemical References

• Aldehydes
• Antineoplastic Agents
• Ligands
• Melanins
• Protease Inhibitors
• Proteasome Inhibitors
• Sulfones

Topics

• Aldehydes (chemistry, metabolism, pharmacology, therapeutic use)
• Antineoplastic Agents (chemistry, metabolism, pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Design
• Humans
• Inhibitory Concentration 50
• Ligands
• Melanins (metabolism)
• Melanoma (drug therapy, pathology)
• Molecular Targeted Therapy
• Protease Inhibitors (chemistry, metabolism, pharmacology, therapeutic use)
• Proteasome Inhibitors
• Sulfones (chemistry, metabolism, pharmacology, therapeutic use)