Characteristic of alkylated chalcones from Angelica keiskei on influenza virus neuraminidase inhibition

As part of our ongoing effort to develop influenza virus neuraminidase (NA) inhibitors from various medicinal plants, we utilized bioassay-guided fractionation to isolated six alkylated chalcones (1-6) from Angelica keiskei. Xanthokeistal A (1) emerged as new compound containing the rare alkyl substitution, 6,6-dimethoxy-3-methylhex-2-enyl. When we tested the ability of these individual alkyl substituted chalcones to inhibit influenza virus NA hydrolysis, we found that 2-hydroxy-3-methyl-3-butenyl alkyl (HMB) substituted chalcone (3, IC(50) = 12.3 mu M) showed most potent inhibitory activity. The order of potency of substituted alkyl groups on for NA inhibition was HMB >6-hydroxyl-3,7-dimethyl-octa-2,7-dienyl > dimethylallyl > geranyl. All NA inhibitors screened were found to be reversible noncompetitive inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.