Design, molecular docking and suppression on NF-κB activity of sinomenine hybrid derivatives.

Abstract

Sinomenine possesses potent suppression on the nuclear factor kappa-B (NF-κB) pathway. The phenylpropanoid moiety was introduced into sinomenine for building dual-structure sinomenine hybrid derivatives. The software AutoDock Vina was used to dock the sinomenine hybrid derivatives with 3 key proteins (1VKX, 4KIK and 6YMN) of NF-κB activation, and the virtually screened derivatives were tested via molecular dynamics simulation. Three series of derivatives were synthesized by Heck cross-coupling reaction, and evaluated for their suppressive effects on NF-κB in HEK 293 cells transfected with plasmid pNF-κB-luc. Some 1-acrylate sinomenine derivatives showed more active suppressive effects than the parent sinomenine. Derivatives 1-3 of sinomenine series were more active on NF-κB than other three series. Derivative 3 with 1-phenethyl acrylate was the most active one.