Probing the anticancer action of novel ferrocene analogues of MNK inhibitors

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 (2126). pp. 1-13. ISSN 1420-3049

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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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
School of Life Sciences > Biochemistry
School of Life Sciences > Chemistry
Subjects: Q Science
Q Science > QD Chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry > QD0411 Organometallic chemistry and compounds
Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: John Spencer
Date Deposited: 24 Aug 2018 14:38
Last Modified: 24 Aug 2018 14:38
URI: http://srodev.sussex.ac.uk/id/eprint/78281

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