Synthesis, radiosynthesis, and biological evaluation of new proteasome inhibitors in a tumor targeting approach.
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.
Vivier
Magali
M
INSERM, UMR 484, Clermont-Ferrand, F-63005, France. mag.viv@free.fr
Rapp
Maryse
M
Papon
Janine
J
Labarre
Pierre
P
Galmier
Marie-Josephe
MJ
Sauzière
Jacques
J
Madelmont
Jean-Claude
JC
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
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