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Bioorganic & Medicinal Chemistry Letters
Article . 2016 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress

Authors: H. Marie Loughran; Ziying Han; Jay E. Wrobel; Sarah E. Decker; Gordon Ruthel; Bruce D. Freedman; Ronald N. Harty; +1 Authors

Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress

Abstract

We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40-Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4.

Related Organizations
Keywords

Dose-Response Relationship, Drug, Molecular Structure, Microbial Sensitivity Tests, Ebolavirus, Antiviral Agents, Vesicular stomatitis Indiana virus, Viral Matrix Proteins, Mice, Structure-Activity Relationship, HEK293 Cells, Marburgvirus, Quinoxalines, Microsomes, Liver, Animals, Cytochrome P-450 CYP3A, Cytochrome P-450 CYP3A Inhibitors, Humans

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    49
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
49
Top 10%
Top 10%
Top 10%
bronze