Docking studies of 1,5-disubtituted tetrazoles analogs of the anticancer drug imatinib as probable inhibitors of the ABL kinase and the T315I mutant kinase

A docking studies of a set of several 1,5-disubstituted tetrazoles (1,5-DS-T) compounds to find potential inhibitors of the Abelson tyrosine-protein kinase (ABL kinase) and the mutated ABL kinase T315I were conducted by using Lamarckian genetic algorithms as search algorithms in Autodock4. Bayesian calculations were performed, and specificity (Sp) and sensitivity (Se) values as well as positive predicted values (PPVs) and negative predicted values (NPVs) were calculated using a set of 99 active ligands and 385 decoys for ABL kinase from the DUD database. RMSD values were calculated between the X-ray crystallographically determined coordinates of the ligands in the complexes of ligand with the ABL kinase and with T315I ABL kinase resistant to imatinib. The predicted results showed the importance of the interactions of the protein with halogens present in some of these 1,5-DS-T ligands. In conclusion, the results suggest that eight novel 1,5-DS-T compounds were identified to be effective inhibitors of ABL kinase.