Probing the anticancer action of novel ferrocene analogues of MNK inhibitors
Probing the anticancer action of novel ferrocene analogues of MNK inhibitors
Two novel ferrocene-containing compounds based upon a known MNK1/2 kinase (MAPK-interacting kinase) inhibitor have been synthesized. The compounds were designed to use the unique shape of ferrocene to exploit a large hydrophobic pocket in MNK1/2 that is only partially occupied by the original compound. Screening of the ferrocene analogues showed that both exhibited potent anticancer effects in several breast cancer and AML (acute myeloid leukemia) cell lines, despite a loss of MNK potency. The most potent ferrocene-based compound 5 was further analysed in vitro in MDA-MB-231 (triple negative breast cancer cells). Dose–response curves of compound 5 for 2D assay and 3D assay generated IC50 values (half maximal inhibitory concentration) of 0.55 µM and 1.25 µM, respectively.
Anticancer, Cell viability, Ferrocene, MNK, Spheroids
Sansook, Supojjanee
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Lineham, Ella
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Hassell-Hart, Storm
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Tizzard, Graham J.
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Coles, Simon J.
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Spencer, John
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Morley, Simon J.
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23 August 2018
Sansook, Supojjanee
b5e89a15-b73e-4b73-b985-e0725f3f4d8a
Lineham, Ella
d00af20b-f6d7-4b92-96c6-0a717d46723a
Hassell-Hart, Storm
cb87c9ec-7c5c-4ba5-8893-1348694eb4bd
Tizzard, Graham J.
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Spencer, John
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Morley, Simon J.
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Sansook, Supojjanee, Lineham, Ella, Hassell-Hart, Storm, Tizzard, Graham J., Coles, Simon J., Spencer, John and Morley, Simon J.
(2018)
Probing the anticancer action of novel ferrocene analogues of MNK inhibitors.
Molecules, 23 (9), [2126].
(doi:10.3390/molecules23092126).
Abstract
Two novel ferrocene-containing compounds based upon a known MNK1/2 kinase (MAPK-interacting kinase) inhibitor have been synthesized. The compounds were designed to use the unique shape of ferrocene to exploit a large hydrophobic pocket in MNK1/2 that is only partially occupied by the original compound. Screening of the ferrocene analogues showed that both exhibited potent anticancer effects in several breast cancer and AML (acute myeloid leukemia) cell lines, despite a loss of MNK potency. The most potent ferrocene-based compound 5 was further analysed in vitro in MDA-MB-231 (triple negative breast cancer cells). Dose–response curves of compound 5 for 2D assay and 3D assay generated IC50 values (half maximal inhibitory concentration) of 0.55 µM and 1.25 µM, respectively.
Text
molecules-23-02126-v3-1
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Accepted/In Press date: 20 August 2018
e-pub ahead of print date: 23 August 2018
Published date: 23 August 2018
Keywords:
Anticancer, Cell viability, Ferrocene, MNK, Spheroids
Identifiers
Local EPrints ID: 424177
URI: http://eprints.soton.ac.uk/id/eprint/424177
PURE UUID: 3e19a8ef-129c-487c-986a-78e679d05283
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Date deposited: 05 Oct 2018 11:33
Last modified: 16 Mar 2024 03:22
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Contributors
Author:
Supojjanee Sansook
Author:
Ella Lineham
Author:
Storm Hassell-Hart
Author:
John Spencer
Author:
Simon J. Morley
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