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Synthesis,molecular modeling and NAD(P)H:quinone oxidoreductase 1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives |
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| Authors: | Mostafa M. Ghorab Mansour S. Alsaid Maureen Higgins Albena T. Dinkova-Kostova Abdelaaty A. Shahat Nehal H. Elghazawy |
| Affiliation: | 1. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia,;2. Department of Drug Radiation Research, National Center for Radiation Research &3. Technology, Atomic Energy Authority, Nasr City, Egypt, mmsghorab@gmail.com;5. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia,;6. Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, UK,;7. Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, UK,;8. Departments of Medicine and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA,;9. Phytochemistry Department, National Research Center, Cairo, Egypt,;10. Zewail City of Science and Technology, Cairo, Egypt, and |
| 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. |
| Keywords: | Cytoprotection Keap1/Nrf2 molecular modeling NQO1 induction 2-phenylquinazolin-4-amine derivatives |