Abstract
Leukemia is a human heterogeneous category of hematological malignancies that is mainly fueled by an imbalanced expression of tyrosine kinases that facilitate uncontrolled cell proliferation and survival. Even though Sorafenib and Regorafenib are proven multi-kinase inhibitors, they are not extensively used in the treatment of leukemia. The purpose of this research was to develop and test some of the modified derivatives of these compounds as possible tyrosine kinase inhibitors to treat leukemia. Molecular docking was performed on 14 derivatives (Sorafenib and S1-S13) with respect to a target of leukemia associated tyrosine kinase. Their therapeutic potential was determined by determining binding affinities (ΔG) and inhibition constants (Ki). S6 (-13.06 kcal/mol, 267.16 pM) had the highest binding affinities and a number of derivatives (S1, S3, S6, and S8) performed better than others. These results indicate that the derivatives modified, especially S6, are good prospects to be further experimentally validated as effective counter-tyrosine kinase inhibitors in the treatment of leukemia.