Inclusion complexation of pinostrobin with various cyclodextrin derivatives

Area of Science:

• Pharmacology and Computational Chemistry
• Natural Products Chemistry
• Supramolecular Chemistry

Background:

• Pinostrobin (PNS), a flavonoid from Southeast Asian herbs, possesses antioxidant, anti-inflammatory, and anticancer properties.
• PNS exhibits very low water solubility, hindering its pharmaceutical applications.
• Beta-cyclodextrin (βCD) and its derivatives are known to improve the solubility and stability of poorly soluble compounds.

Purpose of the Study:

• To investigate the formation and stability of pinostrobin (PNS) inclusion complexes with beta-cyclodextrin (βCD) and its derivatives using molecular dynamics simulations.
• To compare the binding affinities and stability of PNS complexed with βCD, 2,6-dimethyl-βCD (2,6-DMβCD), 2,6-dihydroxypropyl-βCD (2,6-DHPβCD), 2-hydroxypropyl-βCD (2-HPβCD), and 6-hydroxypropyl-βCD (6-HPβCD).

Main Methods:

• Molecular dynamics simulations were employed to model the interactions between PNS and various βCD derivatives.
• Binding free energies were calculated using the molecular mechanics-generalized Born surface area (MM/GBSA) method.
• Complex formation was analyzed based on the orientation of PNS within the βCD cavity (chromone or phenyl ring).

Main Results:

• Pinostrobin (PNS) successfully formed inclusion complexes with βCD and all tested derivatives.
• The stability of the PNS/βCD complexes varied, with the following ranking based on binding free energy: 2,6-DHPβCD > 2,6-DMβCD > 2-HPβCD > 6-HPβCD > βCD.
• The orientation of PNS within the cavity (chromone or phenyl ring) influenced complex stability.
• Simulation results correlated well with experimental solubility data.

Conclusions:

• Beta-cyclodextrin derivatives, particularly 2,6-DHPβCD, significantly enhance the stability of pinostrobin (PNS) inclusion complexes.
• Molecular dynamics simulations provide valuable insights into the binding mechanisms and stability of flavonoid-cyclodextrin complexes.
• These findings suggest potential for using modified cyclodextrins to improve the pharmaceutical utility of poorly soluble flavonoids like PNS.