Panaxadiol and Panaxatriol Derivatives as Anti-Hepatitis B Virus Inhibitors

ABSTRACT: 28 Derivatives of panaxadiol (PD) and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells, of which 17 derivatives inhibited HBV DNA replication. Compounds 4, 9, 10, 14, and 15 showed moderate activity against HBV DNA replication with IC(50) values ranged from 7.27 to 28.21 μM compared with PD. In particular, 3-O-2′-thenoyl panaxadiol (4) inhibited not only HBV DNA replication (IC(50) = 16.5 μM, SI > 115.7) but also HBsAg (IC(50) = 30.8 μM, SI > 62.0) and HBeAg (IC(50) = 18.2 μM, SI > 105.14) secretions. Their structure–activity relationships were discussed for guiding future research toward the discovery of new anti-HBV agents. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13659-014-0018-2) contains supplementary material, which is available to authorized users.