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

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 and1.70 mmol/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 mmol/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.