Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2

Karen A. Nolan; Matthew P. Humphries; John Barnes; Jeremy R. Doncaster; Mary C. Caraher; Nicola Tirelli; Richard A. Bryce; Roger C. Whitehead; Ian J. Stratford

doi:10.1016/j.bmc.2009.11.059

Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2

Karen A. Nolan, Matthew P. Humphries, John Barnes, Jeremy R. Doncaster, Mary C. Caraher, Nicola Tirelli, Richard A. Bryce, Roger C. Whitehead, Ian J. Stratford

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

Abstract

A range of triazoloacridin-6-ones functionalized at C5 and C8 have been synthesized and evaluated for ability to inhibit NQO1 and NQO2. The compounds were computationally docked into the active site of NQO1 and NQO2, and calculated binding affinities were compared with IC50 values for enzyme inhibition. Excellent correlation coefficients were demonstrated suggesting a predictive QSAR model for this series of structurally similar analogues. From this we have identified some of these triazoloacridin-6-ones to be the most potent NQO2 inhibitors so far reported. © 2009 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	696-706
Number of pages	10
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	2
DOIs	https://doi.org/10.1016/j.bmc.2009.11.059
Publication status	Published - 15 Jan 2010

Keywords

Molecular modelling
NQ01
NQ02
Structure-activity relationship
Toxicity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2009.11.059

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title = "Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2",

abstract = "A range of triazoloacridin-6-ones functionalized at C5 and C8 have been synthesized and evaluated for ability to inhibit NQO1 and NQO2. The compounds were computationally docked into the active site of NQO1 and NQO2, and calculated binding affinities were compared with IC50 values for enzyme inhibition. Excellent correlation coefficients were demonstrated suggesting a predictive QSAR model for this series of structurally similar analogues. From this we have identified some of these triazoloacridin-6-ones to be the most potent NQO2 inhibitors so far reported. {\textcopyright} 2009 Elsevier Ltd. All rights reserved.",

keywords = "Molecular modelling, NQ01, NQ02, Structure-activity relationship, Toxicity",

author = "Nolan, {Karen A.} and Humphries, {Matthew P.} and John Barnes and Doncaster, {Jeremy R.} and Caraher, {Mary C.} and Nicola Tirelli and Bryce, {Richard A.} and Whitehead, {Roger C.} and Stratford, {Ian J.}",

year = "2010",

month = jan,

day = "15",

doi = "10.1016/j.bmc.2009.11.059",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry",

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TY - JOUR

T1 - Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2

AU - Nolan, Karen A.

AU - Humphries, Matthew P.

AU - Barnes, John

AU - Doncaster, Jeremy R.

AU - Caraher, Mary C.

AU - Tirelli, Nicola

AU - Bryce, Richard A.

AU - Whitehead, Roger C.

AU - Stratford, Ian J.

PY - 2010/1/15

Y1 - 2010/1/15

N2 - A range of triazoloacridin-6-ones functionalized at C5 and C8 have been synthesized and evaluated for ability to inhibit NQO1 and NQO2. The compounds were computationally docked into the active site of NQO1 and NQO2, and calculated binding affinities were compared with IC50 values for enzyme inhibition. Excellent correlation coefficients were demonstrated suggesting a predictive QSAR model for this series of structurally similar analogues. From this we have identified some of these triazoloacridin-6-ones to be the most potent NQO2 inhibitors so far reported. © 2009 Elsevier Ltd. All rights reserved.

AB - A range of triazoloacridin-6-ones functionalized at C5 and C8 have been synthesized and evaluated for ability to inhibit NQO1 and NQO2. The compounds were computationally docked into the active site of NQO1 and NQO2, and calculated binding affinities were compared with IC50 values for enzyme inhibition. Excellent correlation coefficients were demonstrated suggesting a predictive QSAR model for this series of structurally similar analogues. From this we have identified some of these triazoloacridin-6-ones to be the most potent NQO2 inhibitors so far reported. © 2009 Elsevier Ltd. All rights reserved.

KW - Molecular modelling

KW - NQ01

KW - NQ02

KW - Structure-activity relationship

KW - Toxicity

U2 - 10.1016/j.bmc.2009.11.059

DO - 10.1016/j.bmc.2009.11.059

M3 - Article

C2 - 20036559

SN - 0968-0896

VL - 18

SP - 696

EP - 706

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 2

ER -

Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2

Abstract

Keywords

UN SDGs

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