Design, synthesis, and molecular hybrids of caudatin and cinnamic acids as novel anti-hepatitis B virus agents.
Forty-six conjugated derivatives of caudatin with substituted cinnamic acids were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the derivatives exhibited potent anti-HBV activity, especially inhibiting the HBV DNA replication with the IC(50) values from 2.44 to 22.89 μΜ. Compound 18 showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA replication with IC(50) values of 5.52, 5.52, 2.44 μΜ, respectively, and had good safety (LD(50) > 1250 mg/kg) according to the acute toxicity study. Preliminary mechanism investigation suggested that compound 18 exerted antivirus effects via interfering HBV X promoter and enhancer I to influence HBV transcriptions.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132# Lanhei Road, Heilongtan, Kunming 650201, PR China.
Li-Jun
LJ
Wang
Chang-An
CA
Geng
Yun-Bao
YB
Ma
Jie
J
Luo
Xiao-Yan
XY
Huang
Hao
H
Chen
Ning-Jia
NJ
Zhou
Xue-Mei
XM
Zhang
Ji-Jun
JJ
Chen
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D060326:Chemistry Techniques, Synthetic; D002934:Cinnamates / Q000737:chemistry*; D015195:Drug Design; D005260:Female; D006027:Glycosides / Q000737:chemistry*; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D013256:Steroids / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D002934:Cinnamates; D006027:Glycosides; D013256:Steroids; C570806:caudatin; C029010:cinnamic acid