In Silico Design, Synthesis and Characterization of New Spebrutinib Analogues

Abstract

Background: Recently, in silico or computer-aided drug design has emerged as a cornerstone on the harbor of modern drug discovery. One of the approaches to treat cancer is the inhibition of tyrosine kinase, which is considered as a key enzyme in the survival of the cancerous cells. Spebrutinib, as a member of the tyrosine kinase inhibitors, has few unwanted side effects due to its off-target bindings. In this work, the GOLD program was employed to predict the bindings and thus the inhibitory activity toward the tyrosine kinase. Methodology: After the design and docking processes, the chemical synthesis of three spebrutinib analogues was achieved. Results: The percent yields of the chemical syntheses were ranged from 81% to 89%. These analogues were characterized utilizing; FT-IR, DSC, CHN, and 1H NMR. In conclusion, these new spebrutinib analogues were successfully designed, synthesized, and characterized. However, these analogues are potential anticancer agents and biological activity against cancerous and toxicity pattern against normal cells are crucial to affirm the present findings.