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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.

SUBMITTER: El Aissi R

PROVIDER: S-EPMC4027609 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

El Aissi Radhia R Liu Jianrong J Besse Sophie S Canitrot Damien D Chavignon Olivier O Chezal Jean-Michel JM Miot-Noirault Elisabeth E Moreau Emmanuel E

ACS medicinal chemistry letters 20140220 5

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 mai ...[more]

PMID: 24900863

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