B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2014

B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase

Résumé

Following our recent report showing the potential of naturally occurring aurones (2benzylidenebenzofuran-3(2H)-ones) as anti-hepatitis C virus (HCV) agents, efforts were continued in order to refine the structural requirements for the inhibitory effect on HCV RNA-dependent RNA polymerase (RdRp). In this study, we targeted the Bring moiety of aurones with the aim to improve structural features associated with higher inhibition of the targeted polymerase. In vitro evaluation of the RdRp inhibitory activity of the 37 newly synthesized compounds pointed out that the replacement of the Bring with a N-substituted indole moiety induced the highest inhibitory effect. Of these, compounds 31, 40 and 41 were found to be the most active (IC50 = 2.3-2.4 µM). Docking experiments performed with the most active compounds revealed that the allosteric thumb pocket I of RdRp is the binding pocket for aurone analogues.
Fichier principal
Vignette du fichier
EurJMedChem_Peuchmaur_20140220.pdf (597.72 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04015683 , version 1 (06-03-2023)

Identifiants

Citer

Amel Meguellati, Abdelhakim Ahmed-Belkacem, Wei Yi, Romain Haudecoeur, Marie Crouillère, et al.. B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase. European Journal of Medicinal Chemistry, 2014, 80, pp.579-592. ⟨10.1016/j.ejmech.2014.04.005⟩. ⟨hal-04015683⟩
9 Consultations
24 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More