title: 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.affiliation: INSERM, UMR 484, Clermont-Ferrand, F-63005, France. mag.viv@free.fr
authors.forename: Magali
authors.initials: M
authors.lastname: Vivier
authors.forename: Maryse
authors.initials: M
authors.lastname: Rapp
authors.forename: Janine
authors.initials: J
authors.lastname: Papon
authors.forename: Pierre
authors.initials: P
authors.lastname: Labarre
authors.forename: Marie-Josephe
authors.initials: MJ
authors.lastname: Galmier
authors.forename: Jacques
authors.initials: J
authors.lastname: Sauzière
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Madelmont
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007457:Iodine Radioisotopes; D007930:Leucine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010795:Phthalic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D061988:Proteasome Inhibitors; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014226:Triazenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007457:Iodine Radioisotopes; C528859: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; D009842:Oligopeptides; D010795:Phthalic Acids; D061988:Proteasome Inhibitors; D019275:Radiopharmaceuticals; D014226:Triazenes; D007930:Leucine