EXPLORATION OF HYDROXYL SUBSTITUTED REGORAFENIB DERIVATIVES AS A TYROSINE KINASE INHIBITORS OF LEUKIMIA THROUGH MOLECULAR DOCKING

Abstract

The primary cause of leukemia, a diverse group of hematological cancers in humans, is an imbalance in the expression of tyrosine kinases, which promote unchecked cell growth and survival. Despite being established multi-kinase inhibitors, Regorafenib is not widely utilized to treat leukemia. Investigating hydroxyl-substituted derivatives of Regorafenib as potential tyrosine kinase inhibitors was the aim of this study. Seven (7) derivatives (Regorafenib and R1-R7) were subjected to molecular docking in relation to a leukemia-associated tyrosine kinase target. By calculating binding affinities (ΔG) and inhibition constants (Ki), their therapeutic potential was ascertained. The highest binding affinities were found in R1 (-14.03 kcal/mol, 52.31 pM), and many derivatives (R1, and R7) outperformed the others. These results indicate that the derivatives modified with hydroxyl moiety, especially R1, are good prospects to be further experimentally validated as effective counter-tyrosine kinase inhibitors in the treatment of leukemia.