Molecular insights into complex formation between scandenin and various types of β-cyclodextrin

Abstract

Atomistic molecular dynamics (MD) simulation of the inclusion complexes formation between scandenin, a phytochemical compound found in D. scandens, and five different types of cyclodextrin (CD); β-cyclodextrin (βCD), 2-hydroxypropyl βCD (2-HPβCD), 6-hydroxypropyl βCD (6-HPβCD), 2,6-dimethyl βCD (2,6-DMβCD), and 2,6-dihydroxypropyl βCD (2,6-DHPβCD) were carried out via two possible orientations of the guest molecule. The simulated results revealed that scandenin preferentially located within all the studied βCDs nanocavities by inserting its hydroxyphenyl ring and pyran terminal close to the narrow and wider rims (conf-A), respectively. In another feasible orientation (conf-B), the guest substance was deeply included into the lipophilic cavity of only 6-HPβCD and 2,6-DMβCD, but not in the other cyclodextrins. The favored inclusion formation of scandenin/2,6-DHPβCD occurred when the guest interpolated its hydroxyphenyl terminal into CD hydrophobic interior. Binding free energy calculation based on the MM-PBSA approach indicated that the modified βCDs (except for 2,6-DHPβCD) showed the stronger binding affinity to scandenin than did the parent host molecule. The results could help in selecting suitable βCD derivatives to enhance the stability of such guest molecules prior to in vitro testing.