In silico Approach for Design, Synthesis and Biological Evaluation of Tioxanthone Derivatives as Potential Anticancer Agents

The investigation of thioxanthones involved molecular docking, molecular dynamics simulation, synthesis, and evaluation of their potential as anticancer agents. Molecular docking analyses indicated that 2,4-dichloro-1,3-dihydroxythioxanthone and 2,4-dibromo-1,3-dihydroxythioxanthone had lower binding energies and 4-bromo-1,3-dihydroxythioxanthone had the similar binding energy compared to erlotinib. In 50 ns molecular dynamics simulation, 2,4-dichloro-1,3-dihydroxythioxanthone and 2,4-dibromo-1,3-dihydroxythioxanthone complex exhibited more stability than 4-bromo-1,3-dihydroxythioxanthone and erlotinib, while it had similar stability with doxorubicin. These compounds comply the Lipinski's rule parameters and the minimum required parameters of ADMET. The evaluated anticancer activity of 2,4-dichloro-1,3-dihydroxythioxanthone and 2,4-dibromo-1,3-dihydroxythioxanthone revealed them inactive against cervical cancer (HeLa) and colorectal cancer (WiDr) with IC50 more than 100 μM, however was moderate activity toward breast cancer (T47D) and lung cancer (A549). The selectivity index (SI) values of those compounds (7.71–148.4) passed the parameter SI. Based on these findings, 2,4-dibromo-1,3-dihydroxythioxanthone was the most promising anticancer candidate for T47D cancer cell.