2. Academic Validation
  3. Synthesis, structure-activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents

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

  • Bioorg Med Chem Lett. 2014 May 15;24(10):2353-9. doi: 10.1016/j.bmcl.2014.03.060.
Hao Chen 1,  Yun-Bao Ma 2,  Xiao-Yan Huang 2,  Chang-An Geng 2,  Yong Zhao 1,  Li-Jun Wang 2,  Rui-Hua Guo 2,  Wen-Juan Liang 1,  Xue-Mei Zhang 2,  Ji-Jun Chen 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China.
  • 3 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China. Electronic address: chenjj@mail.kib.ac.cn.
PMID: 24731274 DOI: 10.1016/j.bmcl.2014.03.060
Abstract

Dehydroandrographolide and andrographolide, two natural Diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07μM and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal logP value of 1.78 and logD values. Structure-activity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs.

Keywords

Anti-HBV activity; Dehydroandrographolide and andrographolide derivatives; Octanol–water partition coefficients; Structure–activity relationships.

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