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

作者：Montoir David; Barille Nion Sophie; Tonnerre Alain; Juin Philippe; Duflos Muriel; Bazin Marc Antoine

来源：European Journal of Medicinal Chemistry, 2016, 119: 17-33.

DOI：10.1016/j.ejmech.2016.04.050

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

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.

• 出版日期2016-8-25