Crinamine from Crinum asiaticum var.japonicum inhibits hypoxia inducible factor-1 activity but not activity of hypoxia inducible factor-2

In a search for natural product inhibitors of hypoxia inducible factor-1 (HIF-1) function, crinamine (1), a crinane type alkaloid, showed potent dose dependent inhibition (IC50 = 2.7 mu m) of HIF-1 alpha in a cell-based reporter gene assay. Crinamine (1) was isolated from the aerial parts of Crinum asiaticum var.japonicum together with ly-corine (2), norgalanthamine (3) and epinorgalanthamine (4). The other components (2-4) showed no significant inhibition of HIF-1 alpha induced transcriptional activity.