AIM Curcumin (Cur) a natural phenolic compound, is the major component of turmeric.To improve the its bioavailability, we synthesized series derivatives and investigated the activity of Cur and its derivatives against chronic myeloid leukemia (CML).METHODS CML cell line K562 was used to investigate the effects of Cur and its derivatives and their mechanisms against CML; cell proliferation was assay by MTT; kinase assay by luminescence was used to test BCR-ABL kinase activity; Western blot was performed to test protein level of signal molecules; immunoprecipitation was used to test the co-chaperone complex of Hsp90.RESULTS Cur was a potent inhibitor of proliferation of K562 cells with low toxicity to normal marrow mononuclear cells, and induced cytosolic accumulation of cytochrome c and activities of caspase 3, triggering apoptosis of K562 cells.Cur treatment produced a dose dependent increase in G0/G1 phase and decrease in G2/M phase , consistent with this, cyclin D1, cyclin B1 was deregulated in a dose dependent way.Curcumin inhibited the proliferation and induced apoptosis of K562 cells was correlated with down-regulation of P210bcr/abl and inhibition of tyrosine kinase activity of P210bcr/abl without influence on bcr-abl mRNA level, moreover, Ras/MEKK/SEK/JNK/c-Jun signal transduction pathway were also inhibited by Cur.A mechanistic explanation for these findings was provided in a subsequent study in which it was shown that down-regulation of P210bcr/abl by Cur involves dissociation of the binding of P210bcr/abl with Hsp90/p23 complex.Synergistic effects were observed as combination of Cur and Gleevec on both K562 cells and Gleevec resistant K562/G01 cells.C0806 is one of the derivatives serving as a Cur prodrug.It showed no spontaneous hydrolysis at pH 7.4, but was susceptible to hydrolysis and release Cur by homogenized liver and blood plasma.HPLC-MS analysis showed that the t1/2 and AUC of Cur released by C0806 in plasma were 10-and 20-fold higher than those of Cur, respectively.These characteristics result in a longer retaining time of Cur in mice, therefore it exerts better anti-tumor activity then Cur for CML model in vivo.CONCLUSION The potency of cur and its derivatives against CML warrant further investigation for the treatment of CML.