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Probing the anticancer action of novel ferrocene analogues of MNK inhibitors

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
cb87c9ec-7c5c-4ba5-8893-1348694eb4bd
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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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
a3cf55cd-a4c7-4af6-b16c-96c8fb8c4cf4
Morley, Simon J.
5d1a66af-89f7-4ca5-9596-8ba9a78731bb

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).

Record type: Article

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.

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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
ORCID for Graham J. Tizzard: ORCID iD orcid.org/0000-0002-1577-5779
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

Catalogue record

Date deposited: 05 Oct 2018 11:33
Last modified: 26 Nov 2021 02:45

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Contributors

Author: Supojjanee Sansook
Author: Ella Lineham
Author: Storm Hassell-Hart
Author: Simon J. Coles ORCID iD
Author: John Spencer
Author: Simon J. Morley

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