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

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); beta-cyclodextrin (beta CD), 2-hydroxypropyl beta CD (2-HP beta CD), 6-hydroxypropyl beta CD (6-HP beta CD), 2,6-dimethyl beta CD (2,6-DM beta CD), and 2,6-dihydroxypropyl beta CD (2,6-DHP beta CD) were carried out via two possible orientations of the guest molecule. The simulated results revealed that scandenin preferentially located within all the studied beta CDs 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-HP beta CD and 2,6-DM beta CD, but not in the other cyclodextrins. The favored inclusion formation of scandenin/2,6-DHP beta CD 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 beta CDs (except for 2,6-DHP beta CD) showed the stronger binding affinity to scandenin than did the parent host molecule. The results could help in selecting suitable beta CD derivatives to enhance the stability of such guest molecules prior to in vitro testing. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The atomistic molecular dynamics simulation shows that scandenin tends to form inclusion complexes with different types of cyclodextrin, with some cyclodextrins exhibiting higher inclusivity than others. The calculations indicate that modified cyclodextrins have a stronger binding affinity to scandenin compared to the parent host molecule.