Design, synthesis and preliminary biological evaluation of acridine compounds as potential agents for a combined targeted chemo-radionuclide therapy approach to melanoma.
Various iodo-acridone and acridine carboxamides have been prepared and evaluated as agents for targeted radionuclide and/or chemotherapy for melanoma, due to their structural similarity to benzamides which are known to possess specific affinity for melanin. Three of these carboxamides selected for their in vitro cytotoxic properties were radioiodinated with [(125)I]NaI at high specific activity. Biodistribution studies carried out in B16F0 murine melanoma tumour-bearing mice highlighted that acridone 8f and acridine 9d, presented high, long-lasting tumour concentrations together with an in vivo kinetic profile favourable to application in targeted radionuclide therapy.
Desbois
Nicolas
N
Univ Clermont 1, UFR Pharmacie, Clermont-Ferrand F-63001, France.
Gardette
Maryline
M
Papon
Janine
J
Labarre
Pierre
P
Maisonial
Aurélie
A
Auzeloux
Philippe
P
Lartigue
Claire
C
Bouchon
Bernadette
B
Debiton
Eric
E
Blache
Yves
Y
Chavignon
Olivier
O
Teulade
Jean-Claude
JC
Maublant
Jean
J
Madelmont
Jean-Claude
JC
Moins
Nicole
N
Chezal
Jean-Michel
JM
D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D019169:Jurkat Cells; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D014018:Tissue Distribution
D000166:Acridines; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals