Synthesis, structure-activity relationships and biological evaluation of caudatin derivatives as novel anti-hepatitis B virus agents

A series of caudatin derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the 3-O-substituted caudatin derivatives showed effective anti-HBV activity. Among the tested compounds, six compounds (2e-2h, 2l, 2r) exhibited significantly inhibitory activity against HBV DNA replication with IC(50) values in the range of 2.82-7.48 μM. Interestingly, two compounds (2e, 2f) had potent activity inhibiting not only the secretion of HBsAg (IC(50)=18.68 μM, 21.71 μM), HBeAg (IC(50)=13.16 μM, 33.73 μM), but also HBV DNA replication (IC(50)=7.48 μM, 3.63 μM). The structure-activity relationships (SARs) of caudatin derivatives had been discussed, which were useful for caudatin derivatives to be explored and developed as novel anti-HBV agents.