Molecular dynamics simulations of UC781-cyclodextrins inclusion complexes in aqueous solution

The inclusion complexes of highly potent anti-HIV agent. UC781, with beta-cyclodextrin (beta CD), 2,6-dimethyl-beta-cyclodextrin (M beta CD), and 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) in aqueous solution were investigated by molecular dynamics simulations. Simulations show that the phenyl ring of UC781 is trapped inside CD cavities, while the NH group of UC781 interacts with secondary hydroxyl groups at the wider rim of CDs. The different types of CDs directly affect the binding energy and the stability of the inclusion complexes. M beta CD provides the most stable inclusion complex of UC781 among all CDs in this study due to the effect of methoxy groups (-OCH3) at C2 and C6 positions on the glucopyranose of CDs. Structure analysis of CDs and the orientation of UC781 inside CD cavities as well as the effects of aqueous solution to the inclusion complexes of UC781/CDs are discussed. Results of this study have provided an agreeable output: therefore, a reliable prediction method for other drug/CD inclusion complex formations is introduced. (C) 2012 Elsevier B.V. All rights reserved.