title: Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors.
abstract: A series of substituted coumarins1-10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI50 values at a micromolar level in a diverse set of human cancer cells (GI50 = 2-30 μM) and induced a high apoptosis level in MCF-7 breast cancer cell line. The molecular signature of hsp90 inhibition was assessed by depletion of the Erα hsp90 client protein.
authors.affiliation: University Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Davide
authors.initials: D
authors.lastname: Audisio
authors.affiliation: Institut Galien-Paris Sud, CNRS, UMR 8612, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Délphine
authors.initials: D
authors.lastname: Methy-Gonnot
authors.affiliation: Institut Galien-Paris Sud, CNRS, UMR 8612, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Radanyi
authors.affiliation: Institut Galien-Paris Sud, CNRS, UMR 8612, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
authors.affiliation: Institut Galien-Paris Sud, CNRS, UMR 8612, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Denis
authors.affiliation: Institut Galien-Paris Sud, CNRS, UMR 8612, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Félix
authors.initials: F
authors.lastname: Sauvage
authors.affiliation: Institut Galien-Paris Sud, CNRS, UMR 8612, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Vergnaud-Gauduchon
authors.affiliation: University Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Brion
authors.affiliation: University Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France. Electronic address: samir.messaoudi@u-psud.fr.
authors.forename: Samir
authors.initials: S
authors.lastname: Messaoudi
authors.affiliation: University Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France. Electronic address: mouad.alami@u-psud.fr.
authors.forename: Mouad
authors.initials: M
authors.lastname: Alami
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D061986:MCF-7 Cells; D009675:Novobiocin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D009675:Novobiocin
keywords: 4TCNA; 6BrCaQ; Apoptosis; Cytotoxicity; Hsp90