Synthesis, Cytotoxic Evaluation and Molecular Docking of Bromo-Substituted 1,3,6-Trihydroxyxanthone as Protein Tyrosine Kinase Inhibitor

Abstract

A series of bromo-substituted hydroxyxanthone were synthesized using bromine in glacial acetic acid as a solvent, producing compounds 3 and 5 with 82.1% and 84.2% yield, respectively. In vitro analyses of these two compounds using MMT assay against murine leukemia P388 cell line resulted in IC50 of 2,550 and 3,455 μg/mL and selectivity index of 43.21 and 74.40, respectively. These results indicated that the bromo-substituted hydroxyxanthone compounds could potentially be developed as selective and sensitive anti-cancer agents. Furthermore, through the molecular docking conducted using Discovery Studio, compound 3 exhibited interactions between amino acid residues and protein tyrosine kinase (1T46.pdb). This article provides supporting data that xanthone derivatives can be used as drugs for cancer chemotherapy through the mechanism of how this compound can inhibit protein tyrosine kinase.