Format

Send to

Choose Destination
Eur J Med Chem. 2015 Aug 28;101:780-9. doi: 10.1016/j.ejmech.2015.07.015. Epub 2015 Jul 10.

Synthesis and biological evaluation of novel aromatic-heterocyclic biphenyls as potent anti-leukemia agents.

Author information

1
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province, 710061, PR China.
2
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province, 710061, PR China. Electronic address: zhj8623@mail.xjtu.edu.cn.

Abstract

As a continuation to our previous research, twenty-eight aromatic-heterocyclic biphenyls were designed and synthesized as novel Bcr-Abl inhibitors. The title compounds were investigated for their antiproliferative activities against wild K562 cells and Imatinib-resistant K562 cells (K562R). The results indicated that most of them exhibited potent Bcr-Abl inhibition and moderate antiproliferative potency against K562 cells. Furthermore, three compounds 3, 7 and 21 displayed moderate antiproliferative activities against K562R cells. Molecular docking indicated that 3 bound more tightly with Bcr-Abl(T315I) compared to Bcr-Abl(WT). The higher affinity was consistent with its relatively promising K562R cell growth inhibition. These aromatic-heterocyclic biphenyls could be considered as novel lead compound for optimized as Bcr-Abl(T315I) inhibitors. They provide a good starting point for the further development of novel anti-leukemia agents capable of dealing with clinical acquired resistance against Imatinib.

KEYWORDS:

Bcr–Abl inhibitors; Biphenyls; CML; Resistant

PMID:
26231079
DOI:
10.1016/j.ejmech.2015.07.015
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center