Morin Pier, St-Coeur Patrick-Denis, Doiron Jérémie A, Cormier Marc, Poitras Julie J, Surette Marc E, Touaibia Mohamed
Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, Canada.
Molecules. 2017 Jul 6;22(7):1124. doi: 10.3390/molecules22071124.
Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, ), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH₃) were designed and synthesized. (CAPE, ), but not ferulic acid phenethyl ester (FAPE, ), displayed substantial cytotoxicity against two glioma cell lines. Some but not all selected compounds derived from both (CAPE, ) and (FAPE, ) also displayed cytotoxicity. All CAPE-derived compounds were able to significantly inhibit 5-lipoxygenase (5-LO), however FAPE-derived compounds were largely ineffective 5-LO inhibitors. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds in cancer models and provides additional leads in the development of novel therapeutic strategies in gliomas.
多形性胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，与患者生存期短相关，且治疗选择有限。包括咖啡酸苯乙酯（CAPE）在内的多酚类化合物已在多种癌症类型中研究了其抗癌特性。为了进一步探究这些特性在脑癌细胞中的情况，设计并合成了一系列带有额外氧基团（OH或OCH₃）的咖啡酸和阿魏酸酯。咖啡酸苯乙酯（CAPE）对两种胶质瘤细胞系表现出显著的细胞毒性，而阿魏酸苯乙酯（FAPE）则没有。一些（并非全部）源自咖啡酸苯乙酯（CAPE）和阿魏酸苯乙酯（FAPE）的选定化合物也表现出细胞毒性。所有源自咖啡酸苯乙酯的化合物都能够显著抑制5-脂氧合酶（5-LO），然而源自阿魏酸苯乙酯的化合物在很大程度上是无效的5-LO抑制剂。分子对接揭示了该酶与一些被研究化合物之间新的氢键和π-π相互作用。总体而言，这项工作突出了在癌症模型中探索多酚类化合物的相关性，并为胶质瘤新型治疗策略的开发提供了更多线索。
