NAD(P)H: Quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives

Mostafa M. Ghorab; Mansour S. Alsaid; Marwa G. El-Gazzar; Maureen Higgins; Albena T. Dinkova-Kostova; Abdelaaty A. Shahat

doi:10.3109/14756366.2015.1135913

NAD(P)H: Quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives

Mostafa M. Ghorab (Lead / Corresponding author), Mansour S. Alsaid, Marwa G. El-Gazzar, Maureen Higgins, Albena T. Dinkova-Kostova, Abdelaaty A. Shahat

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Abstract

Fourteen novel 4-aminoquinazoline derivatives 2-15 were designed and synthesized. The structure of the newly synthesized compounds was established on the basis of elemental analyses, IR, (1)H-NMR, (13)C-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.

Original language	English
Pages (from-to)	1369-1374
Number of pages	7
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	31
Issue number	6
Early online date	21 Jan 2016
DOIs	https://doi.org/10.3109/14756366.2015.1135913
Publication status	Published - 2016

Keywords

anilinoquinazoline
molecular modeling
Keap1/Nrf2
cytoprotection
NQO1 induction

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10.3109/14756366.2015.1135913

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title = "NAD(P)H: Quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives",

abstract = "Fourteen novel 4-aminoquinazoline derivatives 2-15 were designed and synthesized. The structure of the newly synthesized compounds was established on the basis of elemental analyses, IR, (1)H-NMR, (13)C-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 = "anilinoquinazoline, molecular modeling, Keap1/Nrf2, cytoprotection, NQO1 induction",

author = "Ghorab, {Mostafa M.} and Alsaid, {Mansour S.} and El-Gazzar, {Marwa G.} and Maureen Higgins and Dinkova-Kostova, {Albena T.} and Shahat, {Abdelaaty A.}",

note = "The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research through the Research Group Project no. RGP-VPP-302. Maureen Higgins and Albena T. Dinkova-Kostova are grateful to Cancer Research, UK, (C20953/A18644) for financial support.",

year = "2016",

doi = "10.3109/14756366.2015.1135913",

language = "English",

volume = "31",

pages = "1369--1374",

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

issn = "1475-6366",

publisher = "Informa Healthcare",

number = "6",

}

TY - JOUR

T1 - NAD(P)H

T2 - Quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives

AU - Ghorab, Mostafa M.

AU - Alsaid, Mansour S.

AU - El-Gazzar, Marwa G.

AU - Higgins, Maureen

AU - Dinkova-Kostova, Albena T.

AU - Shahat, Abdelaaty A.

N1 - The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research through the Research Group Project no. RGP-VPP-302. Maureen Higgins and Albena T. Dinkova-Kostova are grateful to Cancer Research, UK, (C20953/A18644) for financial support.

PY - 2016

Y1 - 2016

N2 - Fourteen novel 4-aminoquinazoline derivatives 2-15 were designed and synthesized. The structure of the newly synthesized compounds was established on the basis of elemental analyses, IR, (1)H-NMR, (13)C-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.

AB - Fourteen novel 4-aminoquinazoline derivatives 2-15 were designed and synthesized. The structure of the newly synthesized compounds was established on the basis of elemental analyses, IR, (1)H-NMR, (13)C-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.

KW - anilinoquinazoline

KW - molecular modeling

KW - Keap1/Nrf2

KW - cytoprotection

KW - NQO1 induction

U2 - 10.3109/14756366.2015.1135913

DO - 10.3109/14756366.2015.1135913

M3 - Article

C2 - 26796666

SN - 1475-6366

VL - 31

SP - 1369

EP - 1374

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

IS - 6

ER -

NAD(P)H: Quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives

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Keywords

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