title: Separation and SAR study of HIF-1alpha inhibitory tubulosines from Alangium cf. longiflorum.
abstract: A crude organic solvent extract of Alangium cf. longiflorum exhibited potent inhibition of hypoxia-induced HIF-1 transcriptional activity in human U251 glioma cells. Dereplication and bioactivity-guided fractionation, including Sephadex LH-20 and chiral HPLC chromatographies, led to the isolation of tubulosine ( 1), 9-desmethyltubulosine ( 2), and isotubulosine ( 3). Structures were verified by complete (1)H and (13)C assignments using 1D- and 2D-NMR techniques. Tubulosine strongly inhibited HIF-1 transcriptional activity, isotubulosine was devoid of activity, and 9-desmethyltubulosine possessed 6-fold less potency than tubulosine.
authors.affiliation: Natural Products Support Group, SAIC-Frederick Inc., NCI Frederick, Frederick, MD 21702, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Klausmeyer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: McCloud
authors.forename: Badarch
authors.initials: B
authors.lastname: Uranchimeg
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: D032604:Alangiaceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D004640:Emetine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D018517:Plant Roots / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C009805:tubulosine; D004640:Emetine