Syntheses of C(18) dibenzocyclooctadiene lignan derivatives as anti-HBsAg and anti-HBeAg agents.
(+)-Gomisin K(3) (1) and kadsurarin (2) were isolated from Schizandra arisanensis and Kadsura matsudai, respectively, and a series of C(18) dibenzocyclooctadiene lignan analogues (5-20) derived from 1 and 2 were synthesized. Esterified derivatives of 1 and 2 were evaluated for inhibitory activity against human type B hepatitis with surface antigen (HBsAg) and e antigen (HBeAg). Most of the analogues (5-8, 10, 12-13) derived from 1 exhibited higher anti-HBsAg effects and lower toxicity, and 6, 7, 8 and 12 also showed higher anti-HBeAg activity. Among these active C(18) dibenzocyclooctadiene lignan analogues, the lignan with a but-3-enoyl group (6) exhibited the most active inhibition.
Kuo
Yao-Haur
YH
National Research Institute of Chinese Medicine, No 155-1, Li-Nong St., Sec. 2, Shih-Pai, Taipei 112, Taiwan. kuoyh@nricm.edu.tw
Wu
Ming-Der
MD
Hung
Chia-Cheng
CC
Huang
Ray-Ling
RL
Yang Kuo
Li-Ming
LM
Shen
Ya-Ching
YC
Ong
Chi-Wi
CW
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006514:Hepatitis B Surface Antigens / Q000187:drug effects*; D006513:Hepatitis B e Antigens / Q000187:drug effects*; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D017705:Lignans