Synthesis and anti-hepatic fibrosis activity of novel matrine tricyclic derivatives
Yongchuang Wang A B # , Hang Yang A B # , Wenming Tang B , Luozhu Zhou A , Chuanhao Wang A C , Anhua Huang A B , Daozuan Zhang A B , Zheng Yao B , Wei Li A D , Wannian Zhang A , Yuelin Wu B , Weiheng Xu A * and Zhenyuan Miao
A *
A
B
C
D
# These authors contributed equally to this work.
Handling Editor: John Wade
Abstract
Matrine, a component derived from traditional Chinese medicine, exhibits diverse pharmacological effects such as anti-hepatic fibrosis. Here we have investigated novel matrine tricyclic derivatives designed by a molecular fusion strategy for anti-fibrotic effects. Among these new compounds, ZM842 indicated potent inhibitory TGF-β transcriptional activity in a dose-dependent manner by a TGF-β/Smads reported gene assay. TGF-β1-stimulated LX-2 cells were treated with compound ZM842, resulting in a reduction of fibrosis markers, including collagen I and α-SMA, as observed at the protein level. Molecular docking disclosed that compound ZM842 may inhibit the activation of hepatic stellate cells (HSCs) by directly interacting with TGF-β1 and SMAD-3 proteins. In summary, our results suggest that compound ZM842 inhibits the TGF-β1 signaling pathway and HSC activation, indicating its potential as an anti-hepatic fibrosis agent.
Keywords: anti-hepatic, drug design, fibrosis, matrine, molecular docking, molecular fusion, synthesis, TGF-β.
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