Novel Irreversible Fluorescent Probes Targeting the 18 kDa Translocator Protein: Synthesis and Biological Characterization

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• 作者：Sabrina Taliani ; Eleonora Da Pozzo ; Marusca Bellandi ; Sara Bendinelli ; Isabella Pugliesi ; Francesca Simorini ; Concettina La Motta ; Silvia Salerno ; Anna Maria Marini ; Federico Da Settimo ; Barbara Cosim
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：May 27, 2010
• 年：2010
• 卷：53
• 期：10
• 页码：4085-4093
• 全文大小：931K
• 年卷期：v.53,no.10(May 27, 2010)
• ISSN：1520-4804

文摘

The 18 kDa translocator protein (TSPO) is a mitochondrial protein whose basal density is altered in several diseases, with the result that the evaluation of its expression levels by means of molecular imaging techniques represents a promising diagnostic approach. Experimental procedures using a labeled ligand often cause loss of the bound probe, and consequently high affinity ligands covalently binding the receptor protein are needed to overcome this problem. We have previously described a series of N,N-dialkyl-(2-phenylindol-3-yl)glyoxylamides as potent and selective TSPO ligands. Starting from these derivatives, we designed novel TSPO irreversible ligands bearing an electrophilic isothiocyanato group (7, 8), together with an irreversible NBD-fluorescent probe (18). The TSPO affinity of the new irreversible ligands was measured on rat tissue homogenates by [³H]Ro 5-4864 radiobinding kinetic assays, all compounds showing high affinities for the target protein. Further biological characterization of the fluorescent irreversible TSPO probe 18 was carried out by using fluorescent spectroscopy in human glioma cells.