J. Nat. Prod., 70 (4), 604 -607, 2007. 10.1021/np060567e S0163-3864(06)00567-2
Web Release Date: February 10, 2007

Copyright © 2007 American Chemical Society and American Society of Pharmacognosy

Anti-HCV Bioactivity of Pseudoguaianolides from Parthenium hispitum

Jin-Feng Hu,* Rupal Patel, Bin Li, Eliane Garo, Grayson W. Hough, Matt G. Goering, Hye-Dong Yoo, Mark O'Neil-Johnson, and Gary R. Eldridge

Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc., 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, and Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, California 92121

Received November 12, 2006

Abstract:

Five new (1-5) and four known (6-9) C14-oxygenated 1-hydroxy-11(13)-pseudoguaien-6,12-olides with potent inhibition of hepatitis C virus (HCV) replication were obtained from Parthenium hispitum via high-throughput natural product chemistry methods. A semipreparative HPLC system was used to purify these compounds. The miniaturization of the structure elucidation and dereplication for the mass-limited samples were performed primarily utilizing a capillary-scale NMR probe. Compounds 2-4 were found to possess in vitro anti-HCV activity in the subgenomic HCV replicon system containing luciferase reporter with significant inhibition above 90% at 2 M concentration.

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