Inclusion complexation of pinostrobin with various cyclodextrin derivatives

Pinostrobin (PNS) is one of the important flavonoids and can be abundantly found in the rhizomes of fingerroot (Boesenbergia rotrunda) and galangal (Alpinia galangal and Alpinia officinarum), the herbal basis of Southeast Asian cooking. Similar to other flavonoids, PNS exhibits anti-oxidative, anti-inflammatory and anti-cancer properties. However, this compound has an extremely low water solubility that limits its use in pharmaceutical applications. Beta-cyclodextrin (beta CD) and its derivatives, 2,6-dimethyl-beta CD (2,6-DM beta CD) and the three hydroxypropyl-beta CDs (2-HP beta CD, 6-HP beta CD and 2,6-DHP beta CD), have unique properties that enhance the stability and solubility of such low-soluble guest molecules. In the present study, molecular dynamics simulations were applied to investigate the dynamics and stability of PNS inclusion complexes with beta CD and its derivatives (2,6-DM beta CD, 2,6-DHP beta CD, 2-HP beta CD and 6-HP beta CD). PNS was able to form complexes with beta CD and all four of its derivatives by either the chromone (C-PNS) or phenyl (P-PNS) ring dipping toward the cavity. According to the molecular mechanics-generalized Born surface area binding free energy values, the stability of the different PNS/beta CD complexes was ranked as 2,6-DHP beta CD > 2,6-DM beta CD > 2-HP beta CD > 6-HP beta CD > beta CD. These theoretical results were in good agreement with the stability constants that had been determined by the solubility method. (C) 2015 Elsevier Inc. All rights reserved.