Article Dans Une Revue Molecules Année : 2022

Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90

Résumé

In the context of our SAR study concerning 6BrCaQ analogues as C-terminal Hsp90 inhibitors, we designed and synthesized a novel series of 3-(heteroaryl)quinolin-2(1H), of types 3, 4, and 5, as a novel class of analogues. A Pd-catalyzed Liebeskind–Srogl cross-coupling was developed as a convenient approach for easy access to complex purine architectures. This series of analogues showed a promising biological effect against MDA-MB231 and PC-3 cancer cell lines. This study led to the identification of the best compounds, 3b (IC50 = 28 µM) and 4e, which induce a significant decrease of CDK-1 client protein and stabilize the levels of Hsp90 and Hsp70 without triggering the HSR response.

Domaines

Fichier principal
Vignette du fichier
molecules-1553213 HALL.pdf (746.62 Ko) Télécharger le fichier

Dates et versions

hal-03855550 , version 1 (16-11-2022)

Licence

Identifiants

Citer

Enrique Larghi, Alexandre Bruneau, Félix Sauvage, Mouad Alami, Juliette Vergnaud-Gauduchon, et al.. Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90. Molecules, 2022, 27 (2), pp.412. ⟨10.3390/molecules27020412⟩. ⟨hal-03855550⟩
66 Consultations
261 Téléchargements

Altmetric

Partager

  • More