School of Chemistry and Molecular Bioscience, and Molecular Horizons, University of Wollongong, Wollongong, NSW, 2522, Australia.
Center for Applied Nuclear Science and Technology, National Nuclear Energy Agency, Bandung, 40132, Indonesia.
ChemMedChem. 2021 Jun 17;16(12):1902-1916. doi: 10.1002/cmdc.202000984. Epub 2021 Mar 24.
A series of fluorescent probes from the 6-chloro-2-phenylimidazo[1,2-a]pyridine-3-yl acetamides ligands featuring the 7-nitro-2-oxa-1,3-diazol-4-yl (NBD) moiety has been synthesized and biologically evaluated for their fluorescence properties and for their binding affinity to the 18-kDa translocator protein (TSPO). Spectroscopic studies including UV/Vis absorption and fluorescence measurements showed that the synthesized fluorescent probes exhibit favorable spectroscopic properties, especially in nonpolar environments. In vitro fluorescence staining in brain sections from lipopolysaccharide (LPS)-injected mice revealed partial colocalization of the probes with the TSPO. The TSPO binding affinity of the probes was measured on crude mitochondrial fractions separated from rat brain homogenates in a [ C]PK11195 radioligand binding assay. All the new fluorescent probes demonstrated moderate to high binding affinity to the TSPO, with affinity (K ) values ranging from 0.58 nM to 3.28 μM. Taking these data together, we propose that the new fluorescent probes could be used to visualize the TSPO.
一系列以 6-氯-2-苯基咪唑并[1,2-a]吡啶-3-基乙酰胺配体为基础、带有 7-硝基-2-氧代-1,3-二唑-4-基（NBD）部分的荧光探针已经被合成，并对其荧光性质及其与 18kDa 转位蛋白（TSPO）的结合亲和力进行了生物学评估。包括紫外/可见吸收和荧光测量在内的光谱研究表明，所合成的荧光探针表现出良好的光谱性质，尤其是在非极性环境中。在脂多糖（LPS）注射小鼠的脑切片中的体外荧光染色显示，探针与 TSPO 部分共定位。探针的 TSPO 结合亲和力通过在大鼠脑匀浆分离的粗线粒体部分的 [ C]PK11195 放射性配体结合测定中进行测量。所有新的荧光探针均表现出对 TSPO 的中等至高亲和力，亲和力（K i）值范围为 0.58 nM 至 3.28 μM。综合这些数据，我们提出这些新的荧光探针可用于可视化 TSPO。
