Molecular docking and pharmacophoric modelling of 1,5-disubstituted tetrazoles as inhibitors of two proteins present in cancer, the ABL and the mutated T315I kinase.

A docking study of a set of several 1,5-disubstituted tetrazoles compounds has been performed to predict the poses of some potential inhibitors of the Abelson tyrosine-protein kinase and the mutated Abelson tyrosine-protein kinase T315I. The study was conducted through Lamarckian genetic algorithms in Autodock4 package. Bayesian calculations were performed; specificity and sensitivity values as well as positive predicted values, and negative predicted values were calculated using a set of 99 known experimentally active ligands and 385 decoys for the Abelson tyrosine-protein kinase from the Directory of Useful Decoys database. Root mean square deviation values were calculated though the X-ray crystallographic data of the bioactive pose of imatinib as reference, and the pose obtained with the above methods. The obtained results show the importance of the protein interactions with the halogens present in some of these 1,5-disubstituted tetrazoles ligands, as well as the presence of some hydrophobic fragments, obtained via the pharmacophoric model, concluding that the eight novels 1,5-disubstituted tetrazoles compounds herein identified, could be effective inhibitors of Abelson tyrosine-protein kinase, using a docking calculations.