Studies On The 3D-QSAR Of Andrographolide Derivatives Inhibiting α-glucosidase And The Structure-activity Relationship For Antioxidation Of The Polyhydroxyphenol Compounds

This thesis consists of two parts. The first part deals with the 3D-QSAR studies on andrographolide derivatives inhibiting α-glucosidase and foundation of the database of glucides and inhibitors of glucosidase. The second part includes discussions on extraction processes, separation methods and structural identifications of chemical constituents in Solynum Larytum Thunb., as well as studies on the structure-activity relationship of the polyhydroxyphenol compounds in Solarium Lyratum Thunb. I. The 3D-QSAR studies on andrographolide derivatives inhibiting α-glucosidaseSo far there have been no reports on the three-dimensional structure of the a-glucosidase, which has been used in the test of the inhibiting its activity by andrographolide derivatives, it is important to build the three-dimensional structure of the a-glucosidase with the homology methods. The sequence of a-glucosidase was obtained from the databank of the National Center for Biotechnology Information (NCBI code: P38158), and it is composed of 584 amino acids. The homology was searched from the PDB databank with BLAST program, and 1U0K was found. Their sequence identity between 1U0K and a-glucosidase is as high as 38%. The Modeler module of the Insight II software was used to build the a-glucosidase model. The final structure was further checked with Profile-3D, and root mean square deviation (RMSD) value between 1U0K and P38158 is 0.42 A. The self-compatibility score for this protein is 237.9 which is higher than the low score 120.2 and close to the top score 267.2. The above results indicate that the homology model is reliable in the current test standard. Protein active sites were analyzed by the Binding Site module. Then, we docked andrographolide derivatives into a-glucosidase with the LigandFit module of the Cerius2 software, investigated their interaction modes. This study suggests that hydrogen bonding and electrostatic interaction are the important characteristic of the interaction between the inhibitors and the a-glucosidase. In the end, three-dimensional quantitative structure- activity relationship(3D-QSAR) between andrographolide derivatives and a-glucosidase was established with the QSAR module. The QSAR model was generated by using MFA method, which has a r2cv (cross-validated) of 0.901 while its r2 (conventional) value is 0.996. The higher r2cv and r2 show that QSAR model is reliable. The conclusions of this study will...