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

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

Research output: Contribution to journalArticle

Abstract

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 (US)
Pages (from-to)1-7
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
DOIs
StateAccepted/In press - Apr 5 2016

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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