Synthesis and Biological Evaluation of New Quinoxaline Derivatives of ICF01012 as Melanoma-Targeting Probes.

Abstract

The aim of this study was the synthesis and pharmacokinetic selection of a best melanin-targeting ligand for addressing anticancer agents to pigmented melanoma. Seven quinoxaline carboxamide derivatives were synthesized and radiolabeled with iodine-125. Biodistribution studies of compounds [ (125) I]1a-g performed in melanoma-bearing mice tumor showed significant tumor uptake (range 2.43-5.68%ID/g) within 1 h after i.v. injection. Fast clearance of the radioactivity from the nontarget organs mainly via the urinary system gave high tumor-to-blood and tumor-to-muscle ratios. Given its favorable clearance and high tumor-melanoma uptake at 72 h, amide 1d was the most promising melanoma-targeting ligand in this series. Compound 1d will be used as building block for the design of new melanoma-selective drug delivery systems.

• Authors: Radhia El Aissi, Jianrong Liu, Sophie Besse, Damien Canitrot, Olivier Chavignon, Jean-Michel Chezal, Elisabeth Miot-Noirault, Emmanuel Moreau
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 5 Issue 5 Pg. 468-73 (May 08 2014) ISSN: 1948-5875 [Print] United States
• PMID: 24900863 (Publication Type: Journal Article)