Insilico Analysis and Docking of Imatinib Derivatives Targeting BCR-ABL Oncoprotein for Chronic Myeloid Leukemia

The BCR-Abloncoprotein with constitutive tyrosine kinase activity plays a pivotal role in the pathogenesis of chronic myeloid leukemia (CML), therefore being an ideal target for the drug development. Imatinibmesylate, a selective tyrosine kinases inhibitor (TKI), has excellent efficacy in the treatment of chronic myeloid leukemia. It has opened the way to the development of additional TKIs against chronic myeloid leukemia, including nilotinib and dasatinib. In this study, computational methods are used to design novel imatinib derivatives and evaluated them for interaction with the Bcr-Abloncoprotein through insilico analysis by using Hyperchem 8.0, Gold 3.01 docking software. Here, from the results, it is reported that 1, 14, 26, ligands are having dock score near to imatinib and modifications to these ligands may result in better ligands than imatinib. The results of Toxicity studies also supported 1, 14, 26, better drug-likeness properties. Ligand 4 has shown higher affinity and better interaction with Bcr-Abloncoprotein than imatinib and any other newly designed molecules, but it had shown mutagenicity and irritancy.