Pigeon Pascal, Wang Yong, Top Siden, Najlaoui Feten, Garcia Alvarez Maria Concepcion, Bignon Jérôme, McGlinchey Michael J, Jaouen Gérard
PSL, Chimie ParisTech , 11 Rue Pierre et Marie Curie, F-75005 Paris, France.
UPMC Univ Paris 6, UMR 8232 CNRS, IPCM, Sorbonne Universités , Place Jussieu, F-75005 Paris, France.
J Med Chem. 2017 Oct 26;60(20):8358-8368. doi: 10.1021/acs.jmedchem.7b00743. Epub 2017 Sep 22.
Ferrociphenols are known to display anticancer properties by original mechanisms dependent on redox properties and generation of active metabolites such as quinone methides. Recent studies have highlighted the positive impact of oxidative stress on chemosensitivity and prognosis of ovarian cancer patients. Ovarian adenocarcinomas are shown to be an excellent model for defining the impact of selected ferrociphenols as new therapeutic drugs for such cancers. This work describes the syntheses and preliminary mechanistic research of unprecedented multitargeting heterocyclic ferrociphenols bearing either a succinimidyl or phthalimidyl group that show exceptional antiproliferative behavior against epithelial ovarian cancer cells resistant to cisplatin. Owing to the failure of the present pharmaceutical options, such as carboplatin a metallodrug based on Pt coordination chemistry, these species may help to overcome the problem of lethal resistance. Currently, ferrociphenolic entities generally operate via apoptotic and senescence pathways. We present here our first results in this new cyclic-imide series.
已知二茂铁苯酚类化合物通过依赖氧化还原特性和生成活性代谢物（如醌甲基化物）的原始机制展现出抗癌特性。最近的研究突出了氧化应激对卵巢癌患者化疗敏感性和预后的积极影响。卵巢腺癌被证明是一个很好的模型，可用于确定所选二茂铁苯酚类化合物作为此类癌症新治疗药物的影响。这项工作描述了前所未有的带有琥珀酰亚胺基或邻苯二甲酰亚胺基的多靶点杂环二茂铁苯酚类化合物的合成及初步机理研究，这些化合物对顺铂耐药的上皮性卵巢癌细胞表现出异常的抗增殖行为。由于目前的药物选择（如基于铂配位化学的金属药物卡铂）效果不佳，这些化合物可能有助于克服致命耐药性问题。目前，二茂铁酚类实体通常通过凋亡和衰老途径发挥作用。我们在此展示了这个新的环状酰亚胺系列的首个研究结果。
