Separation and SAR study of HIF-1alpha inhibitory tubulosines from Alangium cf. longiflorum

Planta Med. 2008 Feb;74(3):258-63. doi: 10.1055/s-2008-1034315. Epub 2008 Feb 26.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alangiaceae / chemistry*
  • Cell Line, Tumor
  • Emetine / analogs & derivatives*
  • Emetine / isolation & purification
  • Emetine / pharmacology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Plant Roots / chemistry
  • Structure-Activity Relationship

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • tubulosine
  • Emetine