title: Synthesis, molecular modeling and NAD(P)H:quinone oxidoreductase 1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives.
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
  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.
authors.affiliation: a Department of Pharmacognosy , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .|b Department of Drug Radiation Research , National Center for Radiation Research & Technology, Atomic Energy Authority , Nasr City , Egypt .
authors.forename: Mostafa M
authors.initials: MM
authors.lastname: Ghorab
authors.affiliation: a Department of Pharmacognosy , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .
authors.forename: Mansour S
authors.initials: MS
authors.lastname: Alsaid
authors.affiliation: c Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee , Dundee , UK .
authors.forename: Maureen
authors.initials: M
authors.lastname: Higgins
authors.affiliation: c Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee , Dundee , UK .|d Departments of Medicine and Pharmacology and Molecular Sciences , Johns Hopkins University School of Medicine , Baltimore , MD , USA .
authors.forename: Albena T
authors.initials: AT
authors.lastname: Dinkova-Kostova
authors.affiliation: a Department of Pharmacognosy , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .|e Phytochemistry Department , National Research Center , Cairo , Egypt .
authors.forename: Abdelaaty A
authors.initials: AA
authors.lastname: Shahat
authors.affiliation: f Zewail City of Science and Technology , Cairo , Egypt , and.
authors.forename: Nehal H
authors.initials: NH
authors.lastname: Elghazawy
authors.affiliation: f Zewail City of Science and Technology , Cairo , Egypt , and.|g Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
authors.forename: Reem K
authors.initials: RK
authors.lastname: Arafa
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D004790:Enzyme Induction; D013058:Mass Spectrometry; D051379:Mice; D008958:Models, Molecular; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis*; D066244:Proton Magnetic Resonance Spectroscopy; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C516488:2-phenylquinazoline; D000588:Amines; D011799:Quinazolines; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
keywords: 2-phenylquinazolin-4-amine derivatives; Cytoprotection; Keap1/Nrf2; NQO1 induction; molecular modeling