Synthesis, molecular modeling and NAD(P)H: quinone oxidoreductase 1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives

Mostafa M. Ghorab (Lead / Corresponding author), Mansour S. Alsaid, Maureen Higgins, Albena T. Dinkova-Kostova, Abdelaaty A. Shahat, Nehal H. Elghazawy, Reem K. Arafa

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    Reactive oxygen species (ROS) play an integral role in the pathogenesis of most diseases. This work presents the design and synthesis of novel 2-phenylquinazolin-4-amine derivatives (2-12) and evaluation of their NAD(P)H:quinone oxidoreductase 1 (NQO1) inducer activity in murine cells. Also, molecular docking of all the new compounds was performed to assess their ability to inhibit Keap1-Nrf2 protein-protein interaction through occupying the Keap1-Nrf2-binding domain which biologically leads to a consequent Nrf2 accumulation and enhanced gene expression of NQO1. Docking results showed that all compounds have the ability to interact with Keap1; however compound 7, the most active compound in this study, showed more interactions with key amino acids.

    Original languageEnglish
    Pages (from-to)1612-1618
    Number of pages7
    JournalJournal of Enzyme Inhibition and Medicinal Chemistry
    Issue number6
    Early online date7 Apr 2016
    Publication statusPublished - Apr 2016



    • 2-phenylquinazolin-4-amine derivatives
    • Cytoprotection
    • Keap1/Nrf2
    • molecular modeling
    • NQO1 induction

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