title: Optimization of troglitazone derivatives as potent anti-proliferative agents: towards more active and less toxic compounds.
abstract: Δ2-Troglitazone derivatives were shown to exhibit anti-proliferative activity in a PPARγ-independent manner. We prepared various compounds in order to increase their potency and decrease their toxicity towards non-malignant primary cultured hepatocytes. Many compounds induced viabilities less than 20% at 10 μM on various cancer cell lines. Furthermore, five of them showed hepatocyte viability of 80% or more at 200 μM. In addition, compounds 17 and 18 exhibited promising maximum tolerated doses on a murine model, enabling future investigations.
authors: Université de Lorraine, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CNRS, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
authors: Andrea
authors: A
authors: Bordessa
authors: Université de Lorraine, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France; CNRS, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France.
authors: Christelle
authors: C
authors: Colin-Cassin
authors: Université de Lorraine, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France; CNRS, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France.
authors: Isabelle
authors: I
authors: Grillier-Vuissoz
authors: Université de Lorraine, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France; CNRS, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France.
authors: Sandra
authors: S
authors: Kuntz
authors: Université de Lorraine, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France; CNRS, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France.
authors: Sabine
authors: S
authors: Mazerbourg
authors: Université de Lorraine, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France; CNRS, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France.
authors: Gauthier
authors: G
authors: Husson
authors: Université de Lorraine, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CNRS, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
authors: Myriam
authors: M
authors: Vo
authors: Université de Lorraine, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France; CNRS, CRAN, UMR 7039, BP 70239, F-54506 Vandœuvre-lès-Nancy Cedex, France.
authors: Stéphane
authors: S
authors: Flament
authors: Université de Franche-Comté, Laboratoire de Toxicologie Cellulaire, EA 4267, 25030 Besançon Cedex, France.
authors: Hélène
authors: H
authors: Martin
authors: Université de Lorraine, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CNRS, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
authors: Yves
authors: Y
authors: Chapleur
authors: Université de Lorraine, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CNRS, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France. Electronic address: michel.boisbrun@univ-lorraine.fr.
authors: Michel
authors: M
authors: Boisbrun
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D015195:Drug Design; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D000077288:Troglitazone
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D045162:Thiazolidinediones; D000077288:Troglitazone
keywords: Cancer; Chromane; Hepatotoxicity; Troglitazone