title: Synthesis and biological activity of simplified denoviose-coumarins related to novobiocin as potent inhibitors of heat-shock protein 90 (hsp90).
abstract: A new series of coumarin inhibitors of hsp90 lacking the noviose moiety as well as substituents on C-7 and C-8 positions of the aromatic ring was synthesised and their hsp90 inhibitory activity has been delineated: for example, their capacity to induce the degradation of client proteins and to inhibit estradiol-induced transcription in human breast cancer cells. In cell proliferation assay, the most active compound 5g was approximately 8 times more potent than the parent novobiocin natural compound.
authors.affiliation: Univ Paris-Sud, CNRS, UMR 8612, Laboratoire de Pharmacologie Cellulaire et Moléculaire des Anticancéreux, Faculté de Pharmacie, IFR 141, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Radanyi
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Le Bras
authors.forename: Samir
authors.initials: S
authors.lastname: Messaoudi
authors.forename: Céline
authors.initials: C
authors.lastname: Bouclier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Peyrat
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Brion
authors.forename: Véronique
authors.initials: V
authors.lastname: Marsaud
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
authors.forename: Mouâd
authors.initials: M
authors.lastname: Alami
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009675:Novobiocin / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D003374:Coumarins; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D009675:Novobiocin; D004958:Estradiol