European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2014-06-02 , DOI: 10.1016/j.ejmech.2014.05.083 Phuhai Nguyen , Nassima Oumata , Flavie Soubigou , Justine Evrard , Nathalie Desban , Pascale Lemoine , Serge Bouaziz , Marc Blondel , Cécile Voisset
Series of 6-aminophenanthridines and related heterocyclic compounds such as benzonaphtyridines were prepared. Reduction of one of the three aromatic rings was also performed. The compounds were first tested for their antiprion activity in a previously described yeast-based colourimetric prion assay. The most potent derivatives were then assayed ex vivo against the mammalian prion PrPSc in a cell-based assay. Several of the new compounds were found more potent than the parent lead 6-aminophenanthridine. The most promising compounds against yeast and mammalian prions were 8-azido-6-aminophenanthridine (3m), and 7,10-dihydrophenanthridin-6-amine (14). In the mammalian cell-based assay, the IC50 of these two compounds were around 5 μM and 1.8 μM, respectively.
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评估6-氨基菲啶和相关杂环的抗pr病毒活性
制备了一系列6-氨基菲啶和相关的杂环化合物,例如苯并萘啶。还进行了三个芳环之一的还原。首先在先前描述的基于酵母的比色病毒测定中测试化合物的抗pr病毒活性。然后在基于细胞的测定中针对哺乳动物病毒PrP Sc离体测定最有效的衍生物。发现几种新化合物比母体铅6-氨基菲啶更有效。对抗酵母和哺乳动物pr病毒最有前景的化合物是8-叠氮基-6-氨基菲啶(3m)和7,10-二氢菲啶-6-胺(14)。在基于哺乳动物细胞的测定中,IC 50 这两种化合物的分别分别约为5μM和1.8μM。