title: Anti-HCV bioactivity of pseudoguaianolides from Parthenium hispitum.
abstract: 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.
authors.affiliation: Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences, Inc., 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, USA. jhu@sequoiasciences.com
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
authors.forename: Rupal
authors.initials: R
authors.lastname: Patel
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Eliane
authors.initials: E
authors.lastname: Garo
authors.forename: Grayson W
authors.initials: GW
authors.lastname: Hough
authors.forename: Matt G
authors.initials: MG
authors.lastname: Goering
authors.forename: Hye-Dong
authors.initials: HD
authors.lastname: Yoo
authors.forename: Mark
authors.initials: M
authors.lastname: O'neil-Johnson
authors.forename: Gary R
authors.initials: GR
authors.lastname: Eldridge
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D045789:Sesquiterpenes, Guaiane; D008156:Luciferases