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NAD(P)H: quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives
Authors:Mostafa M. Ghorab  Mansour S. Alsaid  Marwa G. El-Gazzar  Maureen Higgins  Albena T. Dinkova-Kostova  Abdelaaty A. Shahat
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 and Technology, Atomic Energy Authority, Nasr City, Cairo, Egypt, mmsghorab@gmail.com;4. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia,;5. Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Nasr City, Cairo, Egypt,;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, and;9. Phytochemistry Department, National Research CenterDokki, Cairo, Egypt
Abstract:Fourteen novel 4-aminoquinazoline derivatives 215 were designed and synthesized. The structure of the newly synthesized compounds was established on the basis of elemental analyses, IR, 1H-NMR, 13C-NMR, and mass spectral data. The compounds were evaluated for their potential cytoprotective activity in murine Hepa1c1c7 cells. All of the synthesized compounds showed concentration-dependent ability to induce the cytoprotective enzyme NAD(P)H: quinone oxidoreductase (NQO1) with potencies in the low- to sub-micromolar range. This approach offers an encouraging framework which may lead to the discovery of potent cytoprotective agents.
Keywords:4-aminoquinazoline  cytoprotective  NAD(P)H  synthesis
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