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

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

1 IICiMed - Cibles et Médicaments des Infections et de l'Immunité
2 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers

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.

Domaines: Cancer

David Montoir, Sophie Barillé-Nion, Alain Tonnerre, Philippe Juin, Muriel Duflos, et al.. Novel 1,6-naphthyridin-2(1H)-ones as potential anticancer agents targeting Hsp90.. European Journal of Medicinal Chemistry, 2016, 119, pp.17-33. ⟨10.1016/j.ejmech.2016.04.050⟩. ⟨inserm-01334013⟩