Identification of a new natural camptothecin analogue in targeted screening for HIF-1alpha inhibitors.
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.
Klausmeyer
Paul
P
Natural Products Support Group, SAIC-Frederick, Inc, NCI Frederick, Maryland, USA.
McCloud
Thomas G
TG
Melillo
Giovanni
G
Scudiero
Dominic A
DA
Cardellina
John H
JH
Shoemaker
Robert H
RH
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
D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; D002166:Camptothecin