Design, synthesis and preliminary biological evaluation of acridine compounds as potential agents for a combined targeted chemo-radionuclide therapy approach to melanoma

Nicolas Desbois (1, 2) , Maryline Gardette (1, 2) , Janine Papon (1, 3, 2) , Pierre Labarre (1, 3, 2) , Aurélie Maisonial (1, 3, 2) , Philippe Auzeloux (3, 1, 2) , Claire Lartigue (1, 3, 2) , Bernadette Bouchon (1, 3, 2) , Eric Debiton (1, 3, 2) , Yves Blache (4) , Olivier Chavignon (1, 3, 2) , Jean-Claude Teulade (3, 1, 2) , Jean Maublant (2, 1, 3) , Jean-Claude Madelmont (3, 1, 2) , Nicole Moins (3, 1, 2) , Jean-Michel Chezal (3, 1, 2)

1 Etude Métabolique des Molécules Marquées
2 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
3 IMTV - Imagerie Moléculaire et Thérapie Vectorisée
4 MAPIEM - Laboratoire Matériaux Polymères Interfaces Environnement Marin - EA 4323

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 [125I]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.

Domaines: Chimie thérapeutique; Pharmacologie

Nicolas Desbois, Maryline Gardette, Janine Papon, Pierre Labarre, Aurélie Maisonial, et al.. Design, synthesis and preliminary biological evaluation of acridine compounds as potential agents for a combined targeted chemo-radionuclide therapy approach to melanoma. Bioorganic and Medicinal Chemistry, 2008, 16 (16), pp.7671-7690. ⟨10.1016/j.bmc.2008.07.015⟩. ⟨hal-01494523⟩