2. Academic Validation
  3. Anti-HBV agents. Part 3: preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors

Anti-HBV agents. Part 3: preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors

  • Bioorg Med Chem Lett. 2009 Dec 1;19(23):6659-65. doi: 10.1016/j.bmcl.2009.10.006.
Quan Zhang 1,  Zhi-Yong Jiang,  Jie Luo,  Yun-Bao Ma,  Ji-Feng Liu,  Rui-Hua Guo,  Xue-Mei Zhang,  Jun Zhou,  Wei Niu,  Fei-Fei Du,  Li Li,  Chuan Li,  Ji-Jun Chen
Affiliations

Affiliation

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, PR China.
PMID: 19853440 DOI: 10.1016/j.bmcl.2009.10.006
Abstract

Thirty-two tetra-acylated derivatives of alisol A were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. Among the series of alisol A derivatives examined, five analogues were active against HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion in HepG 2.2.15 cells. These results also provide interesting structure-activity relationships of tetra-acylalisol A derivatives. Compounds tetra-acetyl alisol A (A1), tetra-methoxyacetyl alisol A (A23), and tetra-ethoxyacetyl alisol A (A24) exhibited high activities against secretion of HBsAg with IC(50) values of 0.0048, 0.0044, and 0.014 mM, respectively, HBeAg with IC(50) values of 0.011, 0.012, and 0.018 mM, respectively, and remarkable selective index values SI(HBsAg)>333, SI(HBeAg)>145; SI(HBsAg)=209, SI(HBeAg)=77; and SI(HBsAg)>200, SI(HBeAg)>156, respectively. Additional studies in rats showed that compound A1 has favorable pharmacokinetic prosperities for further development purpose, with elimination half-time (t(1/2)) of 1.63 h and oral bioavailability (F) of 40.9%.

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