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

doi:10.3109/14756366.2016.1158714

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

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

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

260 Downloads (Pure)

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 language	English
Pages (from-to)	1612-1618
Number of pages	7
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	31
Issue number	6
Early online date	7 Apr 2016
DOIs	https://doi.org/10.3109/14756366.2016.1158714
Publication status	Published - Apr 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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10.3109/14756366.2016.1158714

Author Accepted Manuscript
This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Enzyme Inhibition and Medicinal Chemistry on 07/04/2016, available online: http://www.tandfonline.com/10.3109/14756366.2016.1158714
Accepted author manuscript, 617 KB

Cite this

Ghorab, M. M., Alsaid, M. S., Higgins, M., Dinkova-Kostova, A. T., Shahat, A. A., Elghazawy, N. H., & Arafa, R. K. (2016). Synthesis, molecular modeling and NAD(P)H: quinone oxidoreductase 1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1612-1618. https://doi.org/10.3109/14756366.2016.1158714

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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 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 = "2-phenylquinazolin-4-amine derivatives, Cytoprotection, Keap1/Nrf2, molecular modeling, NQO1 induction",

author = "Ghorab, \{Mostafa M.\} and Alsaid, \{Mansour S.\} and Maureen Higgins and Dinkova-Kostova, \{Albena T.\} and Shahat, \{Abdelaaty A.\} and Elghazawy, \{Nehal H.\} and Arafa, \{Reem K.\}",

note = "Maureen Higgins and Albena T. Dinkova-Kostova are also grateful to Cancer Research UK (C20953/A10270 and C20953/A18644) for their financial support.",

year = "2016",

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doi = "10.3109/14756366.2016.1158714",

language = "English",

volume = "31",

pages = "1612--1618",

journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",

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publisher = "Taylor \& Francis",

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Synthesis, molecular modeling and NAD(P)H: quinone oxidoreductase 1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives. / Ghorab, Mostafa M. (Lead / Corresponding author); Alsaid, Mansour S.; Higgins, Maureen et al.
In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 31, No. 6, 04.2016, p. 1612-1618.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synthesis, molecular modeling and NAD(P)H

T2 - quinone oxidoreductase 1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives

AU - Ghorab, Mostafa M.

AU - Alsaid, Mansour S.

AU - Higgins, Maureen

AU - Dinkova-Kostova, Albena T.

AU - Shahat, Abdelaaty A.

AU - Elghazawy, Nehal H.

AU - Arafa, Reem K.

N1 - Maureen Higgins and Albena T. Dinkova-Kostova are also grateful to Cancer Research UK (C20953/A10270 and C20953/A18644) for their financial support.

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - 2-phenylquinazolin-4-amine derivatives

KW - Cytoprotection

KW - Keap1/Nrf2

KW - molecular modeling

KW - NQO1 induction

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DO - 10.3109/14756366.2016.1158714

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SN - 1475-6366

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SP - 1612

EP - 1618

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

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IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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