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Molecules 2018, 23(9), 2126;

Probing the Anticancer Action of Novel Ferrocene Analogues of MNK Inhibitors

Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QJ, UK
Faculty of Science and Technology, Princess of Naradhiwas University, Khok Khian 96000, Thailand
Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QG, UK
UK National Crystallography Service, Chemistry, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK
Both authors would like to be considered as first authors.
Authors to whom correspondence should be addressed.
Received: 26 July 2018 / Revised: 20 August 2018 / Accepted: 20 August 2018 / Published: 23 August 2018
(This article belongs to the Special Issue Ferrocene and Ferrocene-Containing Compounds)
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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. View Full-Text
Keywords: ferrocene; anticancer; MNK; cell viability; spheroids ferrocene; anticancer; MNK; cell viability; spheroids

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Sansook, S.; Lineham, E.; Hassell-Hart, S.; Tizzard, G.J.; Coles, S.J.; Spencer, J.; Morley, S.J. Probing the Anticancer Action of Novel Ferrocene Analogues of MNK Inhibitors. Molecules 2018, 23, 2126.

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