Probing the Anticancer Action of Novel Ferrocene Analogues of MNK Inhibitors

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Supojjanee SansookSimon J Morley

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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Citations

Mar 17, 2020·Chembiochem : a European Journal of Chemical Biology·Matthew AllisonRianne M Lord
Apr 29, 2020·International Journal of Molecular Sciences·Celia Pinto-DíezMaría Elena Martín
Apr 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Valentina RepSilvana Raić-Malić
Apr 24, 2021·European Journal of Medicinal Chemistry·Xin JinTao Jiang
Apr 16, 2021·Chemistry : a European Journal·Nazia Nayeem, Maria Contel
Nov 19, 2021·Journal of Medicinal Chemistry·Bharvi Sharma, Vipan Kumar

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Methods Mentioned

BETA
NMR
column chromatography

Software Mentioned

GraphPad Prism
Celigo Image Cytometer

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