Molecular Docking Approach For Design and Synthesis of Thioxanthone Derivatives as Anticancer Agents

Thioxanthone derivatives were docked, synthesized, and tested for their anticancer activity. The molecular docking results showed that 1-hydroxythioxanthone, 2-chloro-1-hydroxythioxanthone, and 4-chloro-1-hydroxythioxanthone gave lower binding energy than erlotinib demonstrating that those thioxanthones have stronger interaction in the active site of EGFR protein. The addition of one hydroxyl and chloro groups on 1-hydroxythioxanthone greatly enhanced its inhibition in EGFR protein. All thioxanthone derivatives had hydrogen bonding interaction with MET769 residue. The in vitro anticancer assay against all cancer cells (T47D, HeLa, WiDr, A549) revealed that 2-chloro-1-hydroxythioxanthone and 4-chloro-1-hydroxythioxanthone gave lower IC50 than 1-hydroxythioxanthone due to the addition of one chloro substituent. Meanwhile, 1,3-dihydroxythioxanthone exhibited the strongest anticancer activity, as well as the highest selectivity index (3.22–19.55) among the other thioxanthones. Based on these findings, 1,3-dihydroxythioxanthone is a potential anticancer drug candidate for further development in the future.