N-Benzyl-2-(6,8-dichloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N-(6- (7-nitrobenzo[c][1,2,5]oxadiazol-4-ylamino)hexyl)acetamide as a New Fluorescent Probe for Perip
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- 作者：Valentino Laquintana ; Nunzio Denora ; Angela Lopedota ; Hiromi Suzuki ; Makoto Sawada ; Mariangela Serra ; Giovanni Biggio ; Andrea Latrofa ; Giuseppe Trapani ; Gaetano Liso
- 刊名：Bioconjugate Chemistry
- 出版年：2007
- 出版时间：September 2007
- 年：2007
- 卷：18
- 期：5
- 页码：1397 - 1407
- 全文大小：505K
- 年卷期：v.18,no.5(September 2007)
- ISSN：1520-4812
文摘
The aim of this work was to develop new fluorescent probes for the localization and function of the peripheralbenzodiazepine receptor (PBR). This receptor is primarily expressed on the mitochondria, and it is overexpressedin a variety of different states including glioma, breast cancer, Alzeheimer's disease, and activated microglia. Forthe mentioned purpose, imidazopyridine and imidazopyrimidine compounds 5-20 were synthesized, and theiraffinity for PBR was determined. Although some intrinsically fluorescent imidazopyrimidine compounds 12-20possess good binding affinity, they cannot be used for visualizing PBR due to their unfavorable fluorescencecharacteristics. Among the imidazopyridine-7-nitrofurazan conjugates 5-11, compound 10 was the most active,and it was found to stain live Ra2 microglial cells effectively. An in vivo biodistribution study carried out oncompound 10 showed that this imidazopyridine derivative, injected in the carotid artery, is able to penetrate toliver parenchyma, whereas fluorescein isothiocyanate labeled dextran (FITC-dextran), used as a control dye, hardlypenetrated from blood vessels to tissues. On the other hand, as for the distribution to brain, the patterns of stainingwith 10 and FITC-dextran are similar, indicating that both of them hardly penetrate into the brain because of theexistence of the blood-brain barrier. The obtained results indicate that compound 10 represents a new usefulfluorescent probe for visualization of activated microglia and PBR.