Article
1,4-Naphthoquinones potently inhibiting P2X7 receptor activity
Registro en:
R. X. FARIA; et al. 1,4-Naphthoquinones potently inhibiting P2X7 receptor activity. European Journal of Medicinal Chemistry, v.143, p.1361-1372. 2018.
0223-5234
10.1016/j.ejmech.2017.10.033
1768-3254
Autor
Faria, R. X.
Oliveira, F. H.
Salles, J. P.
Oliveira, A. S.
von Ranke, N. L.
Bello, M. L.
Rodrigues, C. R.
Castro, H. C.
Louvis, A. R.
Martins, D. L.
Ferreira, V. F.
Resumen
P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R. Further characterization revealed that AN-03 and AN-04 had greater potency than BBG and A740003 in inhibiting dye uptake, IL-1β release, and carrageenan-induced paw edema in vivo. Moreover, we used electrophysiology and molecular docking analysis for characterizing AN-03 and AN-04 action mechanism. These results suggest 1,4-napthoquinones, mainly AN-04, as potential leads to design new P2X7R blockers and anti-inflammatory drugs. 2030-01-01