title: Synthesis of new troglitazone derivatives: anti-proliferative activity in breast cancer cell lines and preliminary toxicological study.
abstract: Breast cancer is the most prevalent cancer in women. The development of resistances to therapeutic agents and the absence of targeted therapy for triple negative breast cancer motivate the search for alternative treatments. With this aim in mind, we synthesised new derivatives of troglitazone, a compound which was formerly used as an anti-diabetic agent and which exhibits anti-proliferative activity on various cancer cell lines. Among the compounds prepared, some displayed micromolar activity against hormone-dependent and hormone-independent breast cancer cells. Furthermore, the influence of the compounds on the viability of primary cultures of human hepatocytes was evaluated. This enabled us to obtain for the first time interesting structure-toxicity relationships in this family of compounds, resulting in 6b and 8b, which show good anti-proliferative activities and poor toxicity towards hepatocytes, compared to troglitazone.
authors.affiliation: Groupe SUCRES, UMR 7565, Nancy-Université-CNRS, BP 70239, F-54506 Vandoeuvre-lès-Nancy, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Salamone
authors.forename: Christelle
authors.initials: C
authors.lastname: Colin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Grillier-Vuissoz
authors.forename: Sandra
authors.initials: S
authors.lastname: Kuntz
authors.forename: Sabine
authors.initials: S
authors.lastname: Mazerbourg
authors.forename: Stéphane
authors.initials: S
authors.lastname: Flament
authors.forename: Hélène
authors.initials: H
authors.lastname: Martin
authors.forename: Lysiane
authors.initials: L
authors.lastname: Richert
authors.forename: Yves
authors.initials: Y
authors.lastname: Chapleur
authors.forename: Michel
authors.initials: M
authors.lastname: Boisbrun
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002839:Chromans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D018675:Toxicity Tests; D000077288:Troglitazone
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D045162:Thiazolidinediones; D000077288:Troglitazone