Design of thioxanthone derivatives as potential tyrosine kinase inhibitor: A molecular docking study

Abstract

Xanthone derivatives have been well-known for their wide and outstanding bioactivity so far. However, investigation of thioxanthone derivatives and their biological activity is rarely reported. In this work, molecular docking analysis was conducted to evaluate the thioxanthone activity as a tyrosine kinase inhibitor (PDGFR, EGFR). Six thioxanthone derivatives (A-F) were optimized using Gaussian 09 with a semi-empirical method and were docked to the receptor using AutoDock4 software. The free binding energy of thioxanthone derivatives was ranging from-7.10 to-8.57 and-6.23 to-7.25 kcal mol-1 against PDGFR and EGFR. Docking result of all thioxanthone derivatives into PDGFR protein exhibited higher binding energies than that of imatinib, whereas docking result into EGFR protein of all thioxanthone derivatives (except for compound A) gave lower binding energies than that of erlotinib. Among the analyzed compounds, compound 4-iodo-1,3-dihydroxythioxanthone (F) exhibits the lowest binding energy in both tyrosine kinase inhibitors due to its ability to form a Hydrogen bond to the PDGFR receptor with the side chain of Cys673 and the EGFR receptor with the side chain Met796 amino acid residue. This result indicated that compound F has a stronger interaction in tyrosine kinase inhibitor thus promising for a new candidate of anticancer agent.