探究新型 MNK 抑制剂类似物的抗癌作用。

Probing the Anticancer Action of Novel Ferrocene Analogues of MNK Inhibitors.

机构信息

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.

出版信息

Molecules. 2018 Aug 23;23(9):2126. doi: 10.3390/molecules23092126.

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 was further analysed in vitro in MDA-MB-231 (triple negative breast cancer cells). Dose⁻response curves of compound for 2D assay and 3D assay generated IC values (half maximal inhibitory concentration) of 0.55 µM and 1.25 µM, respectively.

已经合成了两种基于已知 MNK1/2 激酶（MAPK 相互作用激酶）抑制剂的新型二茂铁类化合物。这些化合物的设计利用了二茂铁的独特形状，来利用 MNK1/2 中一个大的疏水口袋，而这个口袋仅被原始化合物部分占据。二茂铁类似物的筛选表明，尽管 MNK 的活性丧失，但这两种化合物在几种乳腺癌和 AML（急性髓系白血病）细胞系中都表现出很强的抗癌作用。最有效的基于二茂铁的化合物在 MDA-MB-231（三阴性乳腺癌细胞）中进行了进一步的体外分析。化合物在二维测定和三维测定中的剂量-反应曲线产生的 IC 值（半最大抑制浓度）分别为 0.55 µM 和 1.25 µM。