A New Series of Succinimido-ferrociphenols and Related Heterocyclic Species Induce Strong Antiproliferative Effects, Especially against Ovarian Cancer Cells Resistant to Cisplatin

• Published in: Journal of medicinal chemistry Vol. 60; no. 20; pp. 8358 - 8368
• Main Authors: Pigeon, Pascal, Wang, Yong, Top, Siden, Najlaoui, Feten, Garcia Alvarez, Maria Concepcion, Bignon, Jérôme, McGlinchey, Michael J, Jaouen, Gérard
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.10.2017; Amer Chemical Soc
• Subjects: Apoptosis - drug effects; Cancer; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chemical Sciences; Chemistry, Medicinal; Cisplatin - pharmacology; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Life Sciences; Life Sciences & Biomedicine; Ovarian Neoplasms - pathology; Pharmacology & Pharmacy; Phenols - chemistry; Phenols - pharmacology; Science & Technology; Spectrum Analysis; ELECTROCHEMISTRY; APOPTOSIS; ACTIVATION; NUCLEOSIDE ANALOGS; METABOLISM; FERROCENYL; DERIVATIVES; CYTOTOXICITY; BREAST; FERROQUINE
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.7b00743

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.