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

• Main Authors: HeggoduG. Rohit Kumar, Chethan S. Kumar, Hulihalli N. Kiran Kumar, Gopal M. Advi Rao
• Format: Article
• Language: English
• Published: Elsevier 2017-05-01
• Series: Acta Pharmaceutica Sinica B
• Subjects: DNA intercalator; Molecular docking; Kinase inhibitor; Anticancer drugs; Apoptosis; Chemotherapy
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211383516302696

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.