A theoretical study on the molecular encapsulation of luteolin and pinocembrin with various derivatized beta-cyclodextrins

Luteolin (LL) and pinocembrin (PB) are plant-derived flavonoids predominantly found in many fruits and vegetables showing several biological effects, especially an antioxidant activity. However, the low water solubility of these two compounds limits their use in many pharmaceutical applications. Betacyclodextrin (beta CD) and its derivatives (e.g., methylated (M) and hydroxypropylated (HP) beta CDs) have been extensively used to enhance the stability and solubility of many hydrophobic guest molecules through an encapsulation process into the lipophilic inner cavity. In the present study, the dynamics behavior and the stability of inclusion complexes of two flavonoids LL and PB with beta CDs were studied using all-atom molecular dynamics simulations and MM/PB(GB)SA free energy calculations. The obtained results showed that the van der Waals driven encapsulation of LL and PB could adapt the structure of the beta CDs to become more stable conformers via an enhanced intramolecular hydrogen bond formation on the secondary rim. The structural data and free energy results demonstrated that the phenyl orientation was the preferred binding mode for LL and PB inclusion complexations. In addition, beta CD derivatives, especially HP beta CDs could significantly enhance the stability of both flavonoids better than natural beta CD. (C) 2018 Elsevier B.V. All rights reserved.