Novel 1,6-naphthyridin-2(1H)-ones as potential anticancer agents targeting Hsp90

Eur J Med Chem. 2016 Aug 25:119:17-33. doi: 10.1016/j.ejmech.2016.04.050.

David Montoir ¹, Sophie Barillé-Nion ², Alain Tonnerre ¹, Philippe Juin ², Muriel Duflos ¹, Marc-Antoine Bazin ³

Affiliations

1 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.
2 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.
3 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.

PMID: 27153346 DOI: 10.1016/j.ejmech.2016.04.050

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.

Keywords

1,6-Naphthyridin-2(1H)-ones; Breast cancer; Heat shock protein 90; Hsp90 inhibitors; Novobiocin analogs.

Name
Email *

	Sorry, but the email address you supplied was invalid.