title: Identification of a new natural camptothecin analogue in targeted screening for HIF-1alpha inhibitors.
abstract: Screening to detect compounds that inhibit the HIF-1alpha transcriptional activation pathway identified an extract of Ophiorrhiza trichocarpon for investigation. A high throughput dereplication strategy was employed, involving chromatography with spectral data acquisition supported by bioactivity testing and literature referencing, which led to rapid identification of camptothecin (1) and three analogues (2 - 4) as the active compounds. 9,10-Methylenedioxy-(20S)-camptothecin (4) was found for the first time from a plant.
authors.affiliation: Natural Products Support Group, SAIC-Frederick, Inc, NCI Frederick, Maryland, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Klausmeyer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: McCloud
authors.forename: Giovanni
authors.initials: G
authors.lastname: Melillo
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Scudiero
authors.forename: John H
authors.initials: JH
authors.lastname: Cardellina
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018514:Plant Structures; D019666:Rubiaceae; D012680:Sensitivity and Specificity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; D002166:Camptothecin