Anti-HCV bioactivity of pseudoguaianolides from Parthenium hispitum.
Five new (1-5) and four known (6-9) C14-oxygenated 1alpha-hydroxy-11(13)-pseudoguaien-6beta,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 microM concentration.
Hu
Jin-Feng
JF
Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc., 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, USA. jhu@sequoiasciences.com
Patel
Rupal
R
Li
Bin
B
Garo
Eliane
E
Hough
Grayson W
GW
Goering
Matt G
MG
Yoo
Hye-Dong
HD
O'neil-Johnson
Mark
M
Eldridge
Gary R
GR
D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008923:Missouri; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000998:Antiviral Agents; D045789:Sesquiterpenes, Guaiane; D008156:Luciferases