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Bioorg Med Chem Lett. 2015 Oct 1;25(19):4164-8. doi: 10.1016/j.bmcl.2015.08.013. Epub 2015 Aug 8.

Expanding the structural diversity of Bcr-Abl inhibitors: Hybrid molecules based on GNF-2 and Imatinib.

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School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.


In order to expand the structural diversity of Bcr-Abl inhibitors, twenty hybrids (series E and P) have been synthesized and characterized based on Imatinib and GNF-2. Their biological activities were evaluated in vitro against human leukemia cells. Most compounds exhibited potent antiproliferative activity against K562 cells, especially for compounds E4, E5 and E7. Furthermore, these new hybrids were also screened for Abl kinase inhibitory activity, and some of them inhibited Abl kinase with low micromolar IC50 values. In particular, compound P3 displayed the most potent activity with IC50 value of 0.017 μM comparable with that of Imatinib. Molecular docking studies indicated that these novel hybrids fitted well with the active site of Bcr-Abl. These results suggested the great potential of these compounds as novel Bcr-Abl inhibitors.


Bcr-Abl inhibitors; Bioactivity; Docking; Hybrid molecule

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