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• W2016742942 abstract "In this paper, we report the synthesis and cell-based anti-prion activity of quinacrine analogs derived by replacing the basic alkyl side chain of quinacrine with 4-(4-methylpiperazin-I-yl)phenyl, (1-benzylpiperidin-4-yl) and their structural variants. Several promising analogs were found that have a more favorable anti-prion profile than quinacrine in terms of potency and activity across different prion-infected murine cell models. They also exhibited greater binding affinities for a human prion protein fragment (hPrP121–231) than quinacrine, and had permeabilities on the PAMPA-BBB assay that fall within the range of CNS permeant candidates. When evaluated on bidirectional assays on a Pgp overexpressing cell line, one analog was less susceptible to Pgp efflux activity compared to quinacrine. Taken together, the results point to an important role for the substituted 9-amino side chain attached to the acridine, tetrahydroacridine and quinoline scaffolds. The nature of this side chain influenced cell-based potency, PAMPA permeability and binding affinity to hPrP121–231." @default.
• W2016742942 created "2016-06-24" @default.
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• W2016742942 date "2011-07-01" @default.
• W2016742942 modified "2023-10-01" @default.
• W2016742942 title "Anti-prion activities and drug-like potential of functionalized quinacrine analogs with basic phenyl residues at the 9-amino position" @default.
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• W2016742942 doi "https://doi.org/10.1016/j.ejmech.2011.04.016" @default.
• W2016742942 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21531054" @default.
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