Inhibition of protein kinases by anticancer DNA intercalator, 4-butylaminopyrimido4',5':4,5thieno(2,3-)quinoline.
10.1016/j.apsb.2017.01.001
- Author:
HeggoduG Rohit KUMAR
1
;
Chethan S KUMAR
2
;
Hulihalli N Kiran KUMAR
1
;
Gopal M Advi RAO
1
Author Information
1. Department of Biochemistry, Davangere University, Shivagangotri, Tholahunase, Davangere 577002, India.
2. SS Institute of Medical Sciences and Research Centre, Jnanashankara, Davangere 577005, India.
- Publication Type:Journal Article
- Keywords:
Anticancer drugs;
Apoptosis;
Chemotherapy;
DNA intercalator;
Kinase inhibitor;
Molecular docking
- From:
Acta Pharmaceutica Sinica B
2017;7(3):303-310
- CountryChina
- Language:English
-
Abstract:
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-)quinolines (PTQ) to inhibit different PKs by performing computational docking andscreening. Docking studies revealed that 4-butylaminopyrimido[4',5':4,5]thieno(2,3-)quinoline (BPTQ) has a higher order of interaction with the kinase receptors than other PTQ derivatives.screening confirms that BPTQ inhibits VEGFR1 and CHK2, with the ICvalues 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 ICvalue 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.
