α-Mangostin conjugated amino acids as estrogen receptor alpha (ERα) inhibitor

α-Mangostin is a xanthone-derived compound, which can be isolated from the mangosteen's pericarps. It exhibits potential as an anticancer agent and is known to suppress the growth of breast cancer cells. One of the known drawbacks of utilizing α-mangostin is its low bioavailability and to overcome this problem, structure modifications was performed by conjugating α-mangostin with specific amino acids. Molecular modeling of α-mangostin conjugates with amino acids has been systematically conducted. The pharmacophore modeling results using the Ligand-Based Drug Design approach showed that all conjugates conform to the pharmacophore features. The docking simulation results highlight the ability of Am1Leu conjugate to demonstrate interactions with estragon receptor-α (ERα) with a binding energy of -10.74 kcal/mol. Further analysis through molecular dynamics simulations over a 200 ns timeframe supports the efficacy of Am1Leu against ERα. According to the MMPBSA method for molecular dynamics modeling, the binding affinities of 4-hydroxytamoxifen (ΔG Total = -53.25 kcal/mol) and Am1Leu (ΔG Total = -53.33 kcal/mol) were found to be comparable. This suggests that Am1Leu (leucine at C6 hydroxy group) exhibits a similar binding affinity towards ERα as 4-hydroxytamoxifen. The evidence obtained from this study suggested the viability of Am1Leu as a candidate with a good affinity towards ERα for the targeting of breast cancer.