Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors

Shaoping Wu (1, 2) , Lili Yang (2) , Wenji Sun (2) , Longlong Si (3) , Sulong Xiao (3) , Qi Wang (3) , Luc Dechoux (1) , Serge Thorimbert (1) , Matthieu Sollogoub (1) , Demin Zhou (3) , Yongmin Zhang (1, 2, 4)

1 IPCM - Institut Parisien de Chimie Moléculaire
2 Key Laboratory of Resource Biology and Biotechnology
3 State Key Laboratory of Natural and Biomimetic Drugs
4 Institute for Interdisciplinary Research

Based on classical drug design theory, a novel series of gentiopicroside derivatives was designed and synthesized. All synthesized compounds were then biologically evaluated for their inhibition of influenza virus and anti-HCV activity in vitro. Some of the gentiopicroside derivatives, such as 11a, 13d and 16 showed interesting anti-influenza virus activity with IC 50 at 39.5 µM, 45.2 µM and 44.0 µM, respectively. However, no significant anti-HCV activity was found for all of gentiopicroside derivatives. The preliminary results indicate that modification of the sugar moiety on gentiopicroside was helpful for enhancing the anti-influenza activities. Our works demonstrate the importance of secoiridoid natural products as new leads in the development of potential antiviral inhibitors.

Mots clés: Gentiopicroside derivatives; Antiviral agents; Natural product; Secoiridoid; Anti-influenza virus

Domaines: Chimie thérapeutique

Shaoping Wu, Lili Yang, Wenji Sun, Longlong Si, Sulong Xiao, et al.. Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors. European Journal of Medicinal Chemistry, 2017, 130, pp.308-319. ⟨10.1016/j.ejmech.2017.02.028⟩. ⟨hal-01475948⟩