Synthesis and Biological Activity Evaluation of Podophyllotoxin- Linked Bile Acids Derivatives As Potential Anti-Liver Cancer Agents

•We had designed and synthesized 30 novel podophyllotoxin-linked bile acids derivatives, which had not been reported before.•After conjunction with bile acids, most of the derivatives (IC50 = 0.066–0.831 μM) were more potent against three types of tumor cells than Etoposide (VP-16, IC50 = 4.319–41.080 μM) and exhibited similar activity as doxorubicin (IC50 = 0.230–0.745 μM).•Compound 23 exhibited strong activity against HepG2 cell line (IC50 = 0.188 ± 0.01 μM) than MDCK cell line (IC50 = 4.780 ± 0.50 μM) and the SI (IC50MDCK/IC50HepG2) value of compound 23 was 25.4.•Compound 23 acted as Topo Ⅱ inhibition and induced cell apoptosis with S cell cycle arrest.•Compound 23 showed valid antitumor efficacy at 10 mg/kg by intraperitoneal administration with a tumor inhibition rate of 60.9% in the Hepa1-6 xenograft mice model.