Inhibitory effects of antrodins A-E from Antrodia cinnamomea and their metabolites on hepatitis C virus protease.
Antrodia cinnamomea is a highly valued folk medicine used for liver cancer, a disease often caused by the long term infection of hepatitis C virus (HCV). In the present study, the maleic and succinic acid constituents (antrodins A-E) of this medicinal fungus, the in vivo metabolites of antrodin C and the analogue of one of the metabolites were tested for their inhibitory activity on HCV protease. Most of the compounds showed potent inhibitory activity, with antrodin A being the most potent (IC(50) = 0.9 microg/mL). Antrodin A was isolated as one of the constituents of A. cinnamomea and was also detected as an in vivo metabolite of the major constituent antrodin C. The mode of inhibition for antrodin A on HCV protease was revealed by a Lineweaver-Burk plot as competitive inhibition. These results strongly support the use of this folk medicine for liver cancer and HCV infection which is a global problem.
Phuong
Do Thi
do T
Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Ma
Chao-Mei
CM
Hattori
Masao
M
Jin
Jong Sik
JS
D055491:Antrodia / Q000737:chemistry*; D016174:Hepacivirus / Q000187:drug effects*; D008298:Maleates / Q000494:pharmacology*; D015394:Molecular Structure; D025282:Mycelium / Q000737:chemistry; D011480:Protease Inhibitors / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D008298:Maleates; D011480:Protease Inhibitors; D013386:Succinates; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C030272:maleic acid