Synthesis, molecular modeling and NAD(P)H:quinone oxidoreductase 1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives. (1st November 2016)

• Record Type: Journal Article
• Authors: Ghorab, Mostafa M.; Alsaid, Mansour S.; Higgins, Maureen; Dinkova-Kostova, Albena T.; Shahat, Abdelaaty A.; Elghazawy, Nehal H.; Arafa, Reem K.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 6(2016:Dec.)
• Page Start: 1612
• Page End: 1618
• Publication Date: 2016-11-01
• Subjects: Cytoprotection -- Keap1/Nrf2 -- molecular modeling -- NQO1 induction -- 2-phenylquinazolin-4-amine derivatives; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2016.1158714
• Languages: English
• ISSNs: 1475-6366

Abstract

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 compound7, the most active compound in this study, showed more interactions with key amino acids.