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

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]1...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2014-05, Vol.5 (5), p.468-473
Main Authors: El Aissi, Radhia, Liu, Jianrong, Besse, Sophie, Canitrot, Damien, Chavignon, Olivier, Chezal, Jean-Michel, Miot-Noirault, Elisabeth, Moreau, Emmanuel
Format: Article
Language:English
Subjects:
Chemical Sciences
Coordination chemistry
Letter
Medicinal Chemistry
Organic chemistry
Radiochemistry
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Summary: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml400468x