Study On The Inclusion Of Megestrol Acetate/Prednisolone And Cyclodextrins By Spectroscopic Methods And Computational Analysis

In the thesis, megestrol acetate (MA)/prednisolone (PN) with cyclodextrins were investigated by various spectroscopic methods. Then these results obtained were verified by computational analysis.The steroids have important clinical effect, with poor water solubility. Studying on this kind of inclusion caused for corcern proverbially. We choose MA and PN as the object of study. The inclusion complexes were studied in detail, such as characterization, calculating the equilibrium constants (K) and thermodynamic parameters with different kinds of cyclodextrins. The results showed the inclusion complexes have informed, the K under25℃of each inclusion is614.97M-1,226.3M-1,646.24M-1and1625.15M-1. Besides, the inclusion processes are spontaneous and enthalpy driven. By means of NMR, we fund that the D ring of MA have strong interaction with β-CD and γ-CD, the D ring of PN have interaction with β-CD but A ring with DMβCD.Additionally, the inclusion complexations were simulated by autodock molecular docking to analysis the intreraction between the MA/PN and the cyclodextrins. The modelling results showed that the acting force between MA and β-CD was stronger than the interaction between MA and y-CD; and the interaction between PN and DMβCD was stronger than PN with β-CD. The results obtained by autodock were consistent with the experimental results.Hyperchem MM+method was further adopted to optimize the most stable structure of complexes obtained by autodock method. Finally, in order to study the interaction between host and guest, the NBO analysis was adopted. The results indicated that hydrogen bonding interaction, charge-transfer function and hydrophobic force all play key roles in the inclusion complexes.