title: Novel 1,6-naphthyridin-2(1H)-ones as potential anticancer agents targeting Hsp90.
abstract: Hsp90 is an ATP-dependent chaperone known to be overexpressed in many cancers. This way, Hsp90 is an important target for drug discovery. Novobiocin, an aminocoumarin antibiotic, was reported to inhibit Hsp90 targeting C-terminal domain, and showed anti-proliferative properties, leading to the development of new and more active compounds. Consequently, a new set of novobiocin analogs derived from 1,6-naphthyridin-2(1H)-one scaffold was designed, synthesized and evaluated against two breast cancer cell lines. Subsequently, cell cycle progression and apoptosis were conducted on best candidates, finally Western Blot analysis was performed to measure their ability to induce degradation of Hsp90 client proteins.
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICiMed UPRES EA 1155, UFR de Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.
authors.forename: David
authors.initials: D
authors.lastname: Montoir
authors.affiliation: UMR 892 INSERM/6299 CNRS/Université de Nantes, Team 8 'Cell Survival and Tumor Escape in Breast Cancer', Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Barillé-Nion
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICiMed UPRES EA 1155, UFR de Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Tonnerre
authors.affiliation: UMR 892 INSERM/6299 CNRS/Université de Nantes, Team 8 'Cell Survival and Tumor Escape in Breast Cancer', Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Juin
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICiMed UPRES EA 1155, UFR de Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Duflos
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICiMed UPRES EA 1155, UFR de Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France. Electronic address: marc-antoine.bazin@univ-nantes.fr.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Bazin
mesh_terms: D000588:Amines / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D058990:Molecular Targeted Therapy; D009287:Naphthyridines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D009287:Naphthyridines
keywords: 1,6-Naphthyridin-2(1H)-ones; Breast cancer; Heat shock protein 90; Hsp90 inhibitors; Novobiocin analogs