Mechanistic insight of α-mangostin encapsulation in 2-hydroxypropyl-β-cyclodextrin for solubility enhancement

α-Mangostin is the most abundant compound contained in the mangostin (Garcinia mangostana L.) plant which have been developed and proven to have many promising pharmacological effects. However, the low water solubility of α-mangostin causes limitations in its development in clinical purpose. To increase the solubility of a compound, a method currently being developed is to make drug inclusion complexes using cyclodextrins. This research aimed to use in silico techniques namely molecular docking study and molecular dynamics simulation to explore the molecular mechanism and stability of the encapsulation of α-mangostin using cyclodextrins. Two types of cyclodextrins were used including β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin docked against α-mangostin. From the molecular docking results, it shows that the α-mangostin complex with 2-hydroxypropyl-β-cyclodextrin provides the lowest binding energy value of -7.99 Kcal/mol compared to β-cyclodextrin value of -6.14 Kcal/mol. The α-mangostin complex with 2-hydroxypropyl-β-cyclodextrin also showed good stability based on molecular dynamics simulation during 100 ns. From molecular motion, RDF, Rg, SASA, density, total energy analyzes, this complex shows increased solubility in water and provided good stability. This indicates that the encapsulation of α-mangostin with 2-hydroxypropyl-β-cyclodextrin can increase the solubility of the α-mangostin.Communicated by Ramaswamy H. Sarma.