title: Expanding the structural diversity of Bcr-Abl inhibitors: Hybrid molecules based on GNF-2 and Imatinib.
abstract: 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.
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
authors: Xiaoyan
authors: X
authors: Pan
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
authors: Jinyun
authors: J
authors: Dong
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
authors: Ruili
authors: R
authors: Shao
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
authors: Ping
authors: P
authors: Su
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
authors: Yaling
authors: Y
authors: Shi
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
authors: Jinfeng
authors: J
authors: Wang
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
authors: Langchong
authors: L
authors: He
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C508526:GNF-2 compound; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: Bcr-Abl inhibitors; Bioactivity; Docking; Hybrid molecule