Synthesis, Anticancer Activity, Structure-Activity Relationship, and Molecular Modeling Studies of α-Mangostin Derivatives as hERα Inhibitor.

α-Mangostin is one of the secondary metabolites in mangosteen pericarp, which has been reported to have anti-breast cancer activity. In our previous study, three α-mangostin derivatives were computationally designed as hERα antagonists. In this present study, the designed compounds were synthesized undergoing a benzoylation reaction between α-mangostin with three benzoyl chloride derivatives to produce three derivatives, namely, , , and . The synthesized compounds were then evaluated for their antiproliferative activity against the MCF-7 breast cancer cell model with hERα as the protein target. The assay shows moderate activity (57-126 μM) for all derivatives. The dynamic behaviors of all ligands, including α-mangostin and 4-hydroxytamoxifen (4-OHT), were studied with 100 ns of MD simulation. The structure-activity relationship shows that although it does not entirely concord with the expected design, it can explain the trend of α-mangostin and its derivatives antiproliferative activities against MCF-7, which associates with hERα antagonism.