Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors

Digambar Waiker; Chandrabose  Karthikeyan; Vasanthanathan Poongavanam; Jacob Kongsted; Oliver  Lozach; Laurent Meijer; Piyush  Trivedi

doi:10.1016/j.bmc.2014.01.044

Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors

Digambar Waiker
, Chandrabose Karthikeyan
, Vasanthanathan Poongavanam
, Jacob Kongsted
, Oliver Lozach
, Laurent Meijer
, Piyush Trivedi

Department of Physics, Chemistry and Pharmacy

Rajiv Gandhi Proudyogiki Viswavidyalaya
Protein Phosphorylation and Human Disease Group, Station Biologique, CNRS, 29680 Roscoff, Bretagne

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

A series of novel 4-anilinoquinazoline derivatives (3a-3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer's disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3α/β kinase with IC₅₀ values of 1.5 μM and 3 μM, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3β. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3α/β enzymes with potential therapeutic application in Alzheimer's disease.

Original language	English
Journal	Bioorganic & Medicinal Chemistry
Volume	22
Issue number	6
Pages (from-to)	1909–1915
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2014.01.044
Publication status	Published - 2014

Funding

The authors gratefully acknowledge the Sophisticated Analytical Instrumentation Facility (SAIF); Panjab University, Chandigarh for the NMR spectral analysis of the compounds used in this study. DG wishes to thank AICTE, New Delhi for a postgraduate fellowship. The work was also supported by the EEC FP7-KBBE-2012 BlueGenics grant (LM), ‘Institut National contre le Cancer’ (INCa) GLIOMER program and the ‘Fonds Unique Interministériel’ (FUI) PHARMASEA project (LM).

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title = "Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors",

abstract = "A series of novel 4-anilinoquinazoline derivatives (3a-3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer's disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3α/β kinase with IC₅₀ values of 1.5 μM and 3 μM, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3β. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3α/β enzymes with potential therapeutic application in Alzheimer's disease.",

author = "Digambar Waiker and Chandrabose Karthikeyan and Vasanthanathan Poongavanam and Jacob Kongsted and Oliver Lozach and Laurent Meijer and Piyush Trivedi",

year = "2014",

doi = "10.1016/j.bmc.2014.01.044",

language = "English",

volume = "22",

pages = "1909–1915",

journal = "Bioorganic \& Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier",

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}

Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors. / Waiker, Digambar; Karthikeyan, Chandrabose ; Poongavanam, Vasanthanathan et al.
In: Bioorganic & Medicinal Chemistry, Vol. 22, No. 6, 2014, p. 1909–1915.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors

AU - Waiker, Digambar

AU - Karthikeyan, Chandrabose

AU - Poongavanam, Vasanthanathan

AU - Kongsted, Jacob

AU - Lozach, Oliver

AU - Meijer, Laurent

AU - Trivedi, Piyush

PY - 2014

Y1 - 2014

N2 - A series of novel 4-anilinoquinazoline derivatives (3a-3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer's disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3α/β kinase with IC₅₀ values of 1.5 μM and 3 μM, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3β. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3α/β enzymes with potential therapeutic application in Alzheimer's disease.

AB - A series of novel 4-anilinoquinazoline derivatives (3a-3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer's disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3α/β kinase with IC₅₀ values of 1.5 μM and 3 μM, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3β. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3α/β enzymes with potential therapeutic application in Alzheimer's disease.

U2 - 10.1016/j.bmc.2014.01.044

DO - 10.1016/j.bmc.2014.01.044

M3 - Journal article

C2 - 24530227

SN - 0968-0896

VL - 22

SP - 1909

EP - 1915

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 6

ER -

Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors

Abstract

Funding

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