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]t...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 IC_(50) 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 IC_(50) 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.展开更多
基金supported by grant BT/PR10513/BRB/10/618/2008 to GMA from Department of Biotechnology(DBT),Ministry of Science and Technology,Government of India(New Delhi)HGR was supported by DBT(India)
文摘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 IC_(50) 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 IC_(50) 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.
