Synthesis, biological evaluation, and molecular docking of ent -sauchinone-based amide derivatives with potential anti-invasion and anti-migration activities

Ent-Sauchinone is a bioactive lignan isolated from Saururus chinensis (Lour.) Baill could suppress the migration and invasion of hepatocellular carcinoma (HCC) cells. The study involves the structural modification of ent-sauchinone to augment its inhibitory effect on HCC progression and to investigate the mechanisms involved. In this study, a series of ent-sauchinone based amide derivatives were synthesised and the anticancer activities were evaluated against two hepatoma cell lines. Among them, compound 3 exhibited excellent resistance to migration and invasion by reversing the epithelial-mesenchymal transition (EMT) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expression of matrix metalloproteinases (MMPs). Molecular docking results indicate that compound 3 may exert its inhibitory effect on the progression of liver cancer by acting on the DNA-binding domain of STAT3. These results suggested that compound 3 could be a potential anticancer agent, especially for metastatic cancer therapy.