Inhibition of protein kinases by anticancer DNA intercalator, 4-butylaminopyrimido[4',5'∶4,5] thieno(2,3-b)quinoline

• 来源期刊: 药学学报（英文版）
• 关键词: DNA intercalator Molecular docking Kinase inhibitor Anticancer drugs Apoptosis Chemotherapy
• 年，卷（期）: 2017,（3）
• 页码范围: 303-310
• 页数: 8页
• 语种: 英文

摘要

Targeting protein kinases (PKs) has been a promising strategy in treating cancer,as PKs are key regulators of cell survival and proliferation.Here in this study,we studied the ability of pyrimido [4',5'∶4,5]thieno(2,3-b)quinolines (PTQ) to inhibit different PKs by performing computational docking and in vitro screening.Docking studies revealed that 4-butylaminopyrimido[4',5'∶4,5]thieno(2,3-b) quinoline (BPTQ) has a higher order of interaction with the kinase receptors than other PTQ derivatives.In vitro screening confirms that BPTQ inhibits VEGFR1 and CHK2,with the IC50 values of 0.54 and 1.70 μmol/L,respectively.Further,cytotoxicity of BPTQ was measured by trypan blue assay.Treatment with BPTQ decreased the proliferation of HL-60 cells with an IC50 value of 12 μmol/L and induces apoptosis,as explicated by the fall in the mitochondrial membrane potential,annexin V labeling and increased expression of caspase-3.Taken together,these data suggest that BPTQ possess ability to inhibit PKs and to induce cell death in human promyelocytic leukemia cells.